تفاعل #51465

معادلة التفاعل

HATU

DIEA

piperonylamine

pyrimidine

THF water

LiOH

→

N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]indole-6-carboxamide

المردود 4.0%

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvent was removed in vacuo
2. 2
   أخرىThe solvent was removed in vacuo
3. 3
   workup.DISSOLUTIONdissolved in DMF
4. 4
   أخرىthe solvent was removed in vacuo
5. 5
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2
6. 6
   غسيلwashed with saturated NaHCO3 and brine
7. 7
   تجفيفThe organic layer was dried (MgSO4)
8. 8
   أخرىthe solvent was removed in vacuo
9. 9
   أخرىthe residue was chromatographed (CH2Cl2/MeOH, 19/1)

الإجراء التجريبي

To a solution of indole-5-carboxylic acid (0.50 g, 3.1 mmol) in MeOH (25 mL) was added trimethylsilyldiazomethane until no gas evolution was observed. The solution was concentrated, dissolved in CH2Cl2, and washed with saturated NaHCO3 and brine. The organic layer was dried (MgSO4) and the solvent was removed in vacuo to give 0.54 g of the ester (1H NMR (CDCl3) δ 3.95 (s, 3), 6.63 (s, 1), 7.25 (m, 1), 7.40 (d, 1), 7.95 (d, 1), 8.25-8.4 (br s, 1), 8.45 (s, 1)). The ester (100 mg, 0.58 mmol) was dissolved in DMF (10 mL) and 4-chloro-2-imidazol-1-ylpyrimidine (113 mg, 0.63 mmol) was added. After heating at 60° C. for 18 hours, the solvent was removed in vacuo, the residue was dissolved in CH2Cl2, and washed with saturated NaHCO3 and brine. The organic layer was dried (MgSO4), the solvent was removed in vacuo and the residue was chromatographed (CH2Cl2/MeOH, 19/1) to give 68 mg (37%) of the pyrimidine (1H NMR (CDCl3) δ 3.95 (s, 3), 6.90 (s, 1), 7.25 (m, 2), 7.80 (m, 1), 7.95 (s, 1), 8.10 (d, 1), 8.4 (s, 1), 8.50 (d, 1), 8.70 (m, 2)). The pyrimidine was dissolved in THF/water (1/1) and LiOH (6 mg, 0.21 mmol) was added. After heating at 60° C. for 3 hours, the solvent was removed in vacuo and acidified with methanolic HCl. The solvent was removed in vacuo, dissolved in DMF and treated with HATU (42 mg, 0.11 mmol), DIEA (37 mg, 0.21 mmol), and piperonylamine (26 mL, 0.21 mmol). After stirring for 18 hours, the solvent was removed in vacuo, the residue was dissolved in CH2Cl2, and washed with saturated NaHCO3 and brine. The organic layer was dried (MgSO4), the solvent was removed in vacuo, and the residue was chromatographed (CH2Cl2/MeOH, 19/1) to give 2 mg (4%) of N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]indole-6-carboxamide; 1H NMR (CDCl3) δ 3.75 (s, 2), 5.95 (s, 2), 6.80-6.90 (m, 2), 7.05-7.15 (m, 2), 7.25 (m, 2), 7.75-7.85 (m, 2), 8.00 (s, 2), 8.50-8.60 (m, 2), 8.70-8.80 (m, 1); MS: (439.2 M+H)+.

المصدر