Isonicotinic Acid → 4-(2-Fluorophenyl)-7-(isonicotinamido)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361263노트

반응식

HRID 2361263 반응식
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[F:21])=[CH:13][N:12]=[C:11]([C:22]([NH2:24])=[O:23])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1.[C:25](O)(=[O:32])[C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.CO>[F:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:14]1[C:6]2[C:5]3[C:9](=[CH:10][C:2]([NH:1][C:25](=[O:32])[C:26]4[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=4)=[CH:3][CH:4]=3)[NH:8][C:7]=2[C:11]([C:22]([NH2:24])=[O:23])=[N:12][CH:13]=1

참가 물질

7

반응물 4

HCID 5922Isonicotinic AcidHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 679945367-amino-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

생성물 1

HCID 679956144-(2-Fluorophenyl)-7-(isonicotinamido)-9H-pyrido[3,4-b]indole-1-carboxamide수율 32.5%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 7-amino-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (25 mg, 0.078 mmol), isonicotinic acid (11.53 mg, 0.094 mmol), BOP (49.7 mg, 0.112 mmol), and N-methylmorpholine (0.037 mL, 0.337 mmol) in DMF (0.25 mL) was stirred at room temperature for 1.5 hr. The mixture was diluted with MeOH (1.5 mL) and subjected to prep LC. reverse phase HPLC purification. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution to pH 9. The precipitating product (10.8 mg, 0.025 mmol, 32.5% yield) was collected as a pale solid by suction filtration. LCMS (M+H)+=426.14. 1H NMR (500 MHz, DMSO-d6) δ: 11.95 (s, 1H), 10.96 (s, 1H), 6.80 (m, 2H), 8.44 (s, 1H), 8.33 (s, 1H), 8.27 (s, 1H), 7.89 (m, 2H), 7.79 (s, 1H), 7.71-7.67 (m, 2H), 7.54-7.48 (m, 2H), 7.42 (dd, J1=8.6 Hz, J2=1.9 Hz, 1H), 7.28 (d, J=8.6 Hz, 1H).

후처리

  1. customphase HPLC purification
  2. concentrationThe correct fraction was concentrated under vacuum

출처 및 근거

ORD 기록
ord-7aaeffc64b5e4a67811e8eb06d442a76
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685969B2

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