ethyl 3-isothiocyanatopropanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo to afford crude Compound N-74. The crude Compound N-74 obtained above was dissolved in THF (3 mL) and a solution of LiOH.H2O (126 mg, 3 mmol) in H2O (2 mL) was added slowly at 0° C. The reaction was left for 4 h. The solution was then diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74. 1H-NMR (500 MHz, CD3OD): δ 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.04 (m, 8H), 2.53 (t, J=6.0 Hz, 2H), 2.77 (dd, J=6.5, 14.0 Hz, 1H), 2.94-2.95 (m, 1H), 3.05-3.06 (m, 1H), 3.15-3.17 (m, 1H), 3.67 (broad, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 16.17, 16.30, 17.81, 25.96, 27.39, 27.79, 30.68, 31.57, 32.81, 33.20, 33.90, 34.56, 37.55, 40.80, 40.89, 57.93, 61.05, 121.34, 121.70, 125.48, 132.11, 136.24, 140.52, 173.76, 174.55, 175.68; ES-MS: mass calcd for Chemical Formula: C22H36N2O4S2 456.66. Found (M+) m/z 457.2, (M+Na) m/z 479.2. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo to afford crude Compound N-74 obtained The reaction was left for 4 h washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (159 mg, 1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73. 1H-NMR (500 MHz, CD3OD): δ 1.17 (t, J=5.0 Hz, 3H), 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.06 (m, 8H), 2.54 (t, J=5.0 Hz, 2H), 2.77 (dd, J=5.0, 15.0 Hz, 1H), 2.95-2.96 (m, 1H), 3.05-3.06 (m, 1H), 3.16-3.20 (m, 1H), 3.68 (broad, 2H), 4.06 (q, J=5.0 Hz, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 14.65, 16.19, 16.31, 17.83, 25.97, 27.39, 27.80, 30.70, 33.22, 33.91, 34.80, 40.80, 40.90, 57.89, 61.03, 61.71, 61.93, 121.35, 121.70, 125.16, 132.11, 136.24, 140.52, 173.76, 174.47, 210.16; ES-MS: mass calcd for Chemical Formula: C24H40N2O4S2 484.72. Found (M+) m/z 485.3, (M+Na) m/z 507.3. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo to afford crude Compound N-74. The crude Compound N-74 obtained above was dissolved in THF (3 mL) and a solution of LiOH.H2O (126 mg, 3 mmol) in H2O (2 mL) was added slowly at 0° C. The reaction was left for 4 h. The solution was then diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74. 1H-NMR (500 MHz, CD3OD): δ 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.04 (m, 8H), 2.53 (t, J=6.0 Hz, 2H), 2.77 (dd, J=6.5, 14.0 Hz, 1H), 2.94-2.95 (m, 1H), 3.05-3.06 (m, 1H), 3.15-3.17 (m, 1H), 3.67 (broad, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 16.17, 16.30, 17.81, 25.96, 27.39, 27.79, 30.68, 31.57, 32.81, 33.20, 33.90, 34.56, 37.55, 40.80, 40.89, 57.93, 61.05, 121.34, 121.70, 125.48, 132.11, 136.24, 140.52, 173.76, 174.55, 175.68; ES-MS: mass calcd for Chemical Formula: C22H36N2O4S2 456.66. Found (M+) m/z 457.2, (M+Na) m/z 479.2. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo to afford crude Compound N-74 obtained The reaction was left for 4 h washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (159 mg, 1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73. 1H-NMR (500 MHz, CD3OD): δ 1.17 (t, J=5.0 Hz, 3H), 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.06 (m, 8H), 2.54 (t, J=5.0 Hz, 2H), 2.77 (dd, J=5.0, 15.0 Hz, 1H), 2.95-2.96 (m, 1H), 3.05-3.06 (m, 1H), 3.16-3.20 (m, 1H), 3.68 (broad, 2H), 4.06 (q, J=5.0 Hz, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 14.65, 16.19, 16.31, 17.83, 25.97, 27.39, 27.80, 30.70, 33.22, 33.91, 34.80, 40.80, 40.90, 57.89, 61.03, 61.71, 61.93, 121.35, 121.70, 125.16, 132.11, 136.24, 140.52, 173.76, 174.47, 210.16; ES-MS: mass calcd for Chemical Formula: C24H40N2O4S2 484.72. Found (M+) m/z 485.3, (M+Na) m/z 507.3. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo to afford crude Compound N-74. The crude Compound N-74 obtained above was dissolved in THF (3 mL) and a solution of LiOH.H2O (126 mg, 3 mmol) in H2O (2 mL) was added slowly at 0° C. The reaction was left for 4 h. The solution was then diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74. 1H-NMR (500 MHz, CD3OD): δ 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.04 (m, 8H), 2.53 (t, J=6.0 Hz, 2H), 2.77 (dd, J=6.5, 14.0 Hz, 1H), 2.94-2.95 (m, 1H), 3.05-3.06 (m, 1H), 3.15-3.17 (m, 1H), 3.67 (broad, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 16.17, 16.30, 17.81, 25.96, 27.39, 27.79, 30.68, 31.57, 32.81, 33.20, 33.90, 34.56, 37.55, 40.80, 40.89, 57.93, 61.05, 121.34, 121.70, 125.48, 132.11, 136.24, 140.52, 173.76, 174.55, 175.68; ES-MS: mass calcd for Chemical Formula: C22H36N2O4S2 456.66. Found (M+) m/z 457.2, (M+Na) m/z 479.2. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo to afford crude Compound N-74 obtained The reaction was left for 4 h washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (159 mg, 1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73. 1H-NMR (500 MHz, CD3OD): δ 1.17 (t, J=5.0 Hz, 3H), 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.06 (m, 8H), 2.54 (t, J=5.0 Hz, 2H), 2.77 (dd, J=5.0, 15.0 Hz, 1H), 2.95-2.96 (m, 1H), 3.05-3.06 (m, 1H), 3.16-3.20 (m, 1H), 3.68 (broad, 2H), 4.06 (q, J=5.0 Hz, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 14.65, 16.19, 16.31, 17.83, 25.97, 27.39, 27.80, 30.70, 33.22, 33.91, 34.80, 40.80, 40.90, 57.89, 61.03, 61.71, 61.93, 121.35, 121.70, 125.16, 132.11, 136.24, 140.52, 173.76, 174.47, 210.16; ES-MS: mass calcd for Chemical Formula: C24H40N2O4S2 484.72. Found (M+) m/z 485.3, (M+Na) m/z 507.3. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (159 mg, 1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73. 1H-NMR (500 MHz, CD3OD): δ 1.17 (t, J=5.0 Hz, 3H), 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.06 (m, 8H), 2.54 (t, J=5.0 Hz, 2H), 2.77 (dd, J=5.0, 15.0 Hz, 1H), 2.95-2.96 (m, 1H), 3.05-3.06 (m, 1H), 3.16-3.20 (m, 1H), 3.68 (broad, 2H), 4.06 (q, J=5.0 Hz, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 14.65, 16.19, 16.31, 17.83, 25.97, 27.39, 27.80, 30.70, 33.22, 33.91, 34.80, 40.80, 40.90, 57.89, 61.03, 61.71, 61.93, 121.35, 121.70, 125.16, 132.11, 136.24, 140.52, 173.76, 174.47, 210.16; ES-MS: mass calcd for Chemical Formula: C24H40N2O4S2 484.72. Found (M+) m/z 485.3, (M+Na) m/z 507.3. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (159 mg, 1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound F. 1H-NMR (500 MHz, CD3OD): δ 1.17 (t, J=5.0 Hz, 3H), 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.06 (m, 8H), 2.54 (t, J=5.0 Hz, 2H), 2.77 (dd, J=5.0, 15.0 Hz, 1H), 2.95-2.96 (m, 1H), 3.05-3.06 (m, 1H), 3.16-3.20 (m, 1H), 3.68 (broad, 2H), 4.06 (q, J=5.0 Hz, 2 H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 14.65, 16.19, 16.31, 17.83, 25.97, 27.39, 27.80, 30.70, 33.22, 33.91, 34.80, 40.80, 40.90, 57.89, 61.03, 61.71, 61.93, 121.35, 121.70, 125.16, 132.11, 136.24, 140.52, 173.76, 174.47, 210.16; ES-MS: mass calcd for Chemical Formula: C24H40N2O4S2 484.72. Found (M+) m/z 485.3, (M+Na) m/z 507.3. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by preparative HPLC (220 mg, 45%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo to afford crude Compound N-74. The crude Compound N-74 obtained above was dissolved in THF (3 mL) and a solution of LiOH.H2O (126 mg, 3 mmol) in H2O (2 mL) was added slowly at 0° C. The reaction was left for 4 h. The solution was then diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74. 1H-NMR (500 MHz, CD3OD): δ 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.04 (m, 8H), 2.53 (t, J=6.0 Hz, 2H), 2.77 (dd, J=6.5, 14.0 Hz, 1H), 2.94-2.95 (m, 1H), 3.05-3.06 (m, 1H), 3.15-3.17 (m, 1H), 3.67 (broad, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 16.17, 16.30, 17.81, 25.96, 27.39, 27.79, 30.68, 31.57, 32.81, 33.20, 33.90, 34.56, 37.55, 40.80, 40.89, 57.93, 61.05, 121.34, 121.70, 125.48, 132.11, 136.24, 140.52, 173.76, 174.55, 175.68; ES-MS: mass calcd for Chemical Formula: C22H36N2O4S2 456.66. Found (M+) m/z 457.2, (M+Na) m/z 479.2. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo to afford crude Compound N-74 obtained The reaction was left for 4 h washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (159 mg, 1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73. 1H-NMR (500 MHz, CD3OD): δ 1.17 (t, J=5.0 Hz, 3H), 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.06 (m, 8H), 2.54 (t, J=5.0 Hz, 2H), 2.77 (dd, J=5.0, 15.0 Hz, 1H), 2.95-2.96 (m, 1H), 3.05-3.06 (m, 1H), 3.16-3.20 (m, 1H), 3.68 (broad, 2H), 4.06 (q, J=5.0 Hz, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 14.65, 16.19, 16.31, 17.83, 25.97, 27.39, 27.80, 30.70, 33.22, 33.91, 34.80, 40.80, 40.90, 57.89, 61.03, 61.71, 61.93, 121.35, 121.70, 125.16, 132.11, 136.24, 140.52, 173.76, 174.47, 210.16; ES-MS: mass calcd for Chemical Formula: C24H40N2O4S2 484.72. Found (M+) m/z 485.3, (M+Na) m/z 507.3. washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1) The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by preparative HPLC (220 mg, 45%) to yield Compound N-73