Aniline → HCID 67976399, compound

HRID 1502319Notes

Reaction equation

Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]1([NH:18][C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

Conditions

Temperature: 100 °C

Procedure

N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (200 mg, 0.69 mmol), aniline (76 mg, 0.83 mmol), palladium(II) acetate (30 mg, 0.15 mmol), X-Phos (66 mg, 0.15 mmol) and cesium carbonate (450 mg, 1.4 mmol) were mixed in 1,2-dimethoxyethane (50 mL). After the reaction mixture was stirred at 100° C. under nitrogen for 3 hours, it was concentrated, washed with water and extracted with ethyl acetate, and purified by prep-HPLC to give the desired product (93.2 mg, 44.5%). LCMS (ESI): RT (min)=1.018, M+H+=303.8, Method=A; 1H NMR (400 MHz, DMSO-d6) δ 10.70 (s, 1H), 8.89 (s, 1H), 8.51 (s, 1H), 8.29 (s, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.56 (s, 1H), 7.42 (d, J=8.8 Hz, 1H), 7.30-7.20 (m, 2H), 7.20-7.18 (m, 2H), 6.90-6.89 (m, 1H), 2.05-2.01 (m, 1H), 0.82-0.76 (m, 4H).

Workup

concentrationit was concentrated
washwashed with water
extractionextracted with ethyl acetate
custompurified by prep-HPLC

Sources & evidence

ORD record: ord-595a597994c740a49ac1496dae46f702
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206175B2

Reaction notes

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