2-amino-2-ethylpropane-1,3-diol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Sodium methoxide (2.2 g, Aldrich) was added to a solution of 2-amino-2-ethyl-1,3-propanediol(100.0 g, Aldrich) and diethyl carbonate (169.0 g, Aldrich) This solution was refluxed in a Dean Stark apparatus until no more EtOH was collected. The reaction mixture was cooled, added acetone(200 ml) and allowed to stand overnite at room temperature. The resulting suspension was filtered to give 81.0 g of the desired product as a beige solid. 1H NMR consistent with the proposed structure. was collected The reaction mixture was cooled added acetone(200 ml) to stand overnite at room temperature The resulting suspension was filtered

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Compound (1G) (250 mg, 0.85 mmol) and 2-amino-2-ethyl-1,3-propanediol (298 mg, 2.5 mmol) in NMP (0.25 mL) were stirred at 120° C. for 4 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with EtOAc (2×25 mL). The combined organic layers were dried over sodium sulfate and evaporated in vacuo. The crude product was purified by chromatography (silica gel, CH2Cl2:MeOH, 95:5) to afford 150 mg of the above-titled compound (Example 1). Mp=110-112.9° C. MW (M+H)+=376. extracted with EtOAc (2×25 mL) The combined organic layers were dried over sodium sulfate evaporated in vacuo The crude product was purified by chromatography (silica gel, CH2Cl2:MeOH, 95:5)

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

Procedure: Compound (1G) (250 mg, 0.85 mmol) and 2-amino-2-ethyl-1,3-propanediol (298 mg, 2.5 mmol) in NMP (0.25 mL) were stirred at 120° C. for 4 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with EtOAc (2×25 mL). The combined organic layers were dried over sodium sulfate and evaporated in vacuo. The crude product was purified by chromatography (silica gel, CH2Cl2:MeOH, 95:5) to afford 150 mg of the above-titled compound (Example 1). Mp=110-112.9° C. MW (M+H)+=376. extracted with EtOAc (2×25 mL) The combined organic layers were dried over sodium sulfate evaporated in vacuo The crude product was purified by chromatography (silica gel, CH2Cl2:MeOH, 95:5)

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

Procedure: 26 g (130 mmoles) of dodecanoic acid and 31 g (260 mmoles) of 2-amino-2-ethyl-1,3-propanediol were condensed together by heating at 185°-190° C. for 30 hours. Work up and distillation of the residue at 160°-162° C./1 mm Hg gave 33.19 g (90%) of the product. condensed together by heating at 185°-190° C. for 30 hours Work up and distillation of the residue at 160°-162° C./1 mm Hg

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

Procedure: Sodium methoxide (2.2 g, Aldrich) was added to a solution of 2-amino-2-ethyl-1,3-propanediol(100.0 g, Aldrich) and diethyl carbonate (169.0 g, Aldrich) This solution was refluxed in a Dean Stark apparatus until no more EtOH was collected. The reaction mixture was cooled, added acetone(200 ml) and allowed to stand overnite at room temperature. The resulting suspension was filtered to give 81.0 g of the desired product as a beige solid. 1H NMR consistent with the proposed structure. was collected The reaction mixture was cooled added acetone(200 ml) to stand overnite at room temperature The resulting suspension was filtered

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

Procedure: Compound (1G) (250 mg, 0.85 mmol) and 2-amino-2-ethyl-1,3-propanediol (298 mg, 2.5 mmol) in NMP (0.25 mL) were stirred at 120° C. for 4 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with EtOAc (2×25 mL). The combined organic layers were dried over sodium sulfate and evaporated in vacuo. The crude product was purified by chromatography (silica gel, CH2Cl2:MeOH, 95:5) to afford 150 mg of the above-titled compound (Example 1). Mp=110-112.9° C. MW (M+H)+=376. extracted with EtOAc (2×25 mL) The combined organic layers were dried over sodium sulfate evaporated in vacuo The crude product was purified by chromatography (silica gel, CH2Cl2:MeOH, 95:5)

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

Procedure: N-(1,1-Bis-hydroxymethyl-propyl)-3-(2-fluoro-4-iodo-phenylamino)-isonicotinamide was synthesized according to the procedure for General Method 1, outlined above, starting with 0.33 mmol of 3-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid (intermediate 1) and 0.47 mmol of 2-amino-2-ethyl-propane-1,3-diol. LC/MS [5.93 min; 460 (M+1)] LC/MS [5.93 min; 460 (M+1)]

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

Procedure: N-(1,1-Bis-hydroxymethyl-propyl)-3-(2-fluoro-4-iodo-phenylamino)-isonicotinamide was synthesized according to the procedure for General Method 1, outlined above, starting with 0.33 mmol of 3-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid (intermediate 1) and 0.47 mmol of 2-amino-2-ethyl-propane-1,3-diol. LC/MS [5.93 min; 460 (M+1)] LC/MS [5.93 min; 460 (M+1)]