Dimethylformamide → 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(1-methylcyclobutyl)benzamide

HRID 468738

Reaktionsgleichung

Reaktionsgleichung von HRID 468738
[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[CH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=2[CH3:26])[C:20]([OH:22])=O)[CH:11]=3)=[O:5])[CH2:3][CH2:2]1.[CH3:27][C:28]1([NH2:32])[CH2:31][CH2:30][CH2:29]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C)C=O>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[CH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=2[CH3:26])[C:20]([NH:32][C:28]2([CH3:27])[CH2:31][CH2:30][CH2:29]2)=[O:22])[CH:11]=3)=[O:5])[CH2:2][CH2:3]1

Komponenten

8

Edukt 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 14988399(1-Methylcyclobutyl)amineHCID 679746613-(3-(Cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylbenzoic acid

Produkt 1

HCID 679747373-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(1-methylcyclobutyl)benzamideAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylbenzoic acid (41.0 mg, 0.118 mmol), 1-methylcyclobutylamine (22.5 mg, 0.264 mmol), (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (81.1 mg, 0.156 mmol), N,N-diisopropylethylamine (64 uL, 0.37 mmol), 4-dimethylaminopyridine (2.89 mg, 0.0237 mmol), and N,N-dimethylformamide (2.0 mL, 26 mmol) was stirred at 50° C. for 15 hours. The reaction mixture was poured into ethyl acetate and washed with water and brine, filtered through a plug of silica gel, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 23.3 mg (78%) of 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(1-methylcyclobutyl)benzamide. LCMS (ESI): RT (min)=5.083, M+H=414.2, method=E; 1H NMR (400 MHz, DMSO) δ 10.90 (s, 1H), 9.19 (s, 1H), 8.51 (s, 1H), 8.35 (s, 1H), 8.04 (s, 1H), 7.94 (d, J=8.5 Hz, 1H), 7.82 (s, 1H), 7.80 (d, J=7.9 Hz, 1H), 7.73 (dd, J=8.5, 1.5 Hz, 1H), 7.41 (d, J=7.9 Hz, 1H), 2.40-2.29 (m, 5H), 2.13-2.04 (m, 1H), 2.03-1.92 (m, 2H), 1.86-1.75 (m, 2H), 1.47 (s, 3H), 0.91-0.80 (m, 4H).

Aufarbeitung

  1. washwashed with water and brine
  2. filtrationfiltered through a plug of silica gel
  3. customevaporated in vacuo
  4. customThe crude product was purified via reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-ba1cf57abb574b34a691560396452fc2
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623889B2

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