Ethanol → HCID 67974814, compound

HRID 1502277Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)=[C:4]([CH3:24])[C:3]=1[F:25].C(O)C.C(=O)(O)[O-].[Na+]>[Pd]>[F:25][C:3]1[C:4]([CH3:24])=[C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]([CH:21]4[CH2:22][CH2:23]4)=[O:20])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:6]=[N:7][CH:2]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of N-(7-(6-chloro-5-fluoro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide (180.0 mg, 0.5059 mmol) in ethanol (10 mL, 200 mmol) was added sodium bicarbonate (95.2 mg, 1.13 mmol) and palladium (60.1 mg, 0.0565 mmol) (10 wt % on carbon). The reaction vessel was purged first with nitrogen and then hydrogen, and then stirred under a hydrogen balloon at 40° C. for 12 hours. The reaction mixture was then filtered through celite and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 77.3 mg (48%) of N-(7-(5-fluoro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (Min)=4.130, M+H=322.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.20 (s, 1H), 8.55 (s, 1H), 8.52 (s, 1H), 8.42 (s, 1H), 8.12 (s, 1H), 7.98 (d, J=8.5 Hz, 1H), 7.76 (dd, J=8.5, 1.4 Hz, 1H), 2.26 (d, J=1.8 Hz, 3H), 2.15-2.03 (m, 1H), 0.94-0.75 (m, 4H).

Workup

customThe reaction vessel was purged first with nitrogen
filtrationThe reaction mixture was then filtered through celite
customevaporated in vacuo
customThe crude product was purified via reverse phase HPLC

Sources & evidence

ORD record: ord-5d8e2c15203542cb9e37eab9f718a7c3
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206175B2

Reaction notes

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