ethyl 5-amino-1H-indole-2-carboxylate

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

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

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

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

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: In like manner to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, the reaction of 2-chloro-5-fluoro-N4-(3-hydroxyphenyl)-4-pyrimidineamine with 2-ethoxycarbony-5-aminoindole gave N2-(2-ethoxycarbonylindol-5-yl)-5-fluoro-N4-(3-hydroxyphenyl)-2,4-pyrimidinediamine. 1H NMR (CD3OD): δ 7.95 (d, 1H), 7.84 (d, 1H, J=3.9 Hz), 7.34 (s, 1H), 7.33 (d, 1H, J=1.8 Hz), 7.22-7.19 (m, 2H), 7.11-7.05 (m, 2H), 6.55 (m, 1H), 4.62 (s, 2H), 4.38 (q, 1H, J=6.9 Hz), 1.40 9t, 3H, J=7.5 Hz). In like manner to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine

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

Procedure: In like manner to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, 2-chloro-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-4-pyrimidineamine and 2-ethoxycarbonyl-5-aminoindole were reacted to yield N2-(2-ethoxycarbonylindol-5-yl)-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine. 1H NMR (CDCl3): δ 7.84 (d, 1H, J=5.4 Hz), 7.76 (d, 1H, J=3.6 Hz), 7.50 (d, 1H, J=9 Hz), 7.23-7.15 (m, 3H), 7.03 (bd, 1H, J=8.7 Hz), 6.78 (d, 1H, J=8.7 Hz), 4.38 (q, 2H, J=7.2 Hz), 4.22 (s, 4H), 1.41 (t, 3H, J=6.9 Hz); LCMS: ret. time: 23.58 min; purity: 100%; MS (m/e): 451 (MH+). were reacted

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

Procedure: In like manner to the preparation of N2,N4-bis(3-hydroxyphenyl)-5-fluoro-2,4-pyrimidinediamine, 2,4-dichloro-5-fluoropyrimidine and 2-ethoxycarbonyl-5-indoleamine were reacted to yield N2,N4-bis(2-ethoxycarbonylindol-5-yl)-5-fluoro-2,4-pyrimidinediamine. 1H NMR (DMSO-d6): δ 11.83 (s, 1H), 11.63 (s, 1H), 9.21 (s, 1H), 8.99 (s, 1H), 8.08 (s, 1H), 8.01 (m, 2H), 7.49-7.22 (m, 4H), 6.92 (s, 1H), 6.63 (s, 1H), 4.29 (q, 4H, J=7.2 Hz), 1.32 (m, 6H); LCMS: ret. time: 24.74 min.; purity: 99%; MS (m/e): 503 (MH+). were reacted

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

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

Procedure: A mixture of 0.204 g (1 mmol) 5-amino-1H-indole-2-carboxylic acid ethyl ester, 133 mg (1 mmol) 1-ethyl piperidone and 0.35 ml (1 mmol) titanium(IV)isopropoxide in 1 ml methanol was treated after 3 h at room temperature with 0.023 g (1 mmol) sodium borohydride and the mixture was allowed to react during 16 h at room temperature. The mixture was poured on 50 ml ice/water and treated with 50 ml ethyl acetate and 5 ml 1 N NaOH aq. After 20 min the mixture was filtered through decalite and the aqueous phase was extracted with 50 ml ethyl acetate. The combined organic phases were washed with 50 ml NaCl sat., dried over Na2SO4 and after filtration evaporated to dryness. The residue was purified over silica eluting with a gradient of dichloromethane (DCM)/2N NH3 in methanol and 0.240 g (76%) of the title compound were isolated as brown solid. MS (m/e): 316.1 (MH+, 100%). to react during 16 h at room temperature was filtered through decalite the aqueous phase was extracted with 50 ml ethyl acetate The combined organic phases were washed with 50 ml NaCl sat. dried over Na2SO4 after filtration evaporated to dryness The residue was purified over silica eluting with a gradient of dichloromethane (DCM)/2N NH3 in methanol

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

Procedure: A mixture of 0.204 g (1 mmol) 5-amino-1H-indole-2-carboxylic acid ethyl ester, 133 mg (1 mmol) 1-ethyl piperidone and 0.35 ml (1 mmol) titanium(IV)isopropoxide in 1 ml methanol was treated after 3 h at room temperature with 0.023 g (1 mmol) sodium borohydride and the mixture was allowed to react during 16 h at room temperature. The mixture was poured on 50 ml ice/water and treated with 50 ml ethyl acetate and 5 ml 1 N NaOH aq. After 20 min the mixture was filtered through decalite and the aqueous phase was extracted with 50 ml ethyl acetate. The combined organic phases were washed with 50 ml NaCl sat., dried over Na2SO4 and after filtration evaporated to dryness. The residue was purified over silica eluting with a gradient of dichloromethane (DCM)/2N NH3 in methanol and 0.240 g (76%) of the title compound were isolated as brown solid. MS (m/e): 316.1 (MH+, 100%). to react during 16 h at room temperature was filtered through decalite the aqueous phase was extracted with 50 ml ethyl acetate The combined organic phases were washed with 50 ml NaCl sat. dried over Na2SO4 after filtration evaporated to dryness The residue was purified over silica eluting with a gradient of dichloromethane (DCM)/2N NH3 in methanol