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

HRID 2361263Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2361263
[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

Komponenten

7

Edukt 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

Produkt 1

HCID 679956144-(2-Fluorophenyl)-7-(isonicotinamido)-9H-pyrido[3,4-b]indole-1-carboxamideAusbeute 32,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-7aaeffc64b5e4a67811e8eb06d442a76
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08685969B2

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