Sodium hydride → HCID 178490766, compound

HRID 2402592

Reaction equation

Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([OH:9])[CH2:5][CH2:4]1.[H-].[Na+].F[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[CH3:23])[C:19](=[O:24])[N:18]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[CH:17]=[CH:16]2>CC(N(C)C)=O>[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([O:9][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][C:22]=2[CH3:23])[C:19](=[O:24])[N:18]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[CH:17]=[CH:16]3)[CH2:5][CH2:4]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 1.48 g (9.75 mmol) of trans-4-aminocyclohexanol hydrochloride in 20 ml of dimethylacetamide where added 1.95 g (48.77 mmol) of sodium hydride (60%) and the mixture was stirred for 15 minutes. Subsequently 2.90 g (9.75 mmol) of 6-fluoro-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one in 30 ml of dimethylacetamide were added and the reaction mixture was heated to 80° C. for 2 days. After cooling the mixture was poured into 300 ml of ice water and the precipitated crude product was purified by chromatography. First the remaining starting material was eluted with ethyl acetate/heptane (2:1) and finally the desired product was eluted by pure methanol giving 1.98 g 6-(trans-4-amino-cyclohexyloxy)-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one.

Workup

temperatureAfter cooling the mixture
customthe precipitated crude product
customwas purified by chromatography
washwas eluted with ethyl acetate/heptane (2:1)
washfinally the desired product was eluted by pure methanol giving 1.98 g 6-(trans-4-amino-cyclohexyloxy)-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one

Sources & evidence

ORD record: ord-630dc1f4e5af4792bd1ae0834f2fe0f1
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796458B2

Linked notes

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