Trifluoroacetic acid → 8-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-N,N-dimethyl-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide

HRID 577525Notes

Reaction equation

C([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:22]([C:26]([N:28]([CH3:30])[CH3:29])=[O:27])=[CH:21][C:20]([O:31][CH:32]([CH3:34])[CH3:33])=[C:19]([Cl:35])[C:18]=3[C:17]2=[O:36])=[C:13]([CH3:37])[CH:12]=[C:11]([CH3:38])[N:10]=1)C1C=CC=CC=1.C(O)(C(F)(F)F)=O>>[Cl:35][C:19]1[C:18]2[C:17](=[O:36])[N:16]([CH2:15][C:14]3[C:9](=[O:8])[NH:10][C:11]([CH3:38])=[CH:12][C:13]=3[CH3:37])[CH2:25][CH2:24][C:23]=2[C:22]([C:26]([N:28]([CH3:30])[CH3:29])=[O:27])=[CH:21][C:20]=1[O:31][CH:32]([CH3:34])[CH3:33]

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 867237512-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-N,N-dimethyl-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide

Product 1

HCID 867237528-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-N,N-dimethyl-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxamideYield 85%

Procedure

A solution of 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-N,N-dimethyl-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide (90b, 16 mg, 89% yield) and TFA (1.5 mL) was stirred at room temperature for 24 hours. The volatiles were removed under vacuum and the residue was purified by preparative HPLC to give the title compound (Example 90, 11 mg, 85% yield) as a white solid. 1H NMR (700 MHz, DMSO-d6) δ 7.15 (s, 1H) 5.90 (s, 1H) 4.65-4.71 (m, 1H) 4.56 (br. s., 2H) 2.98 (s, 3H) 2.76 (s, 3H) 2.57 (br. s, 2H) 2.17 (s, 3H) 2.13 (s, 3H) 1.28 (s, 3H) 1.28 (s, 3H); MS: 446.1 [M+1].

Workup

customThe volatiles were removed under vacuum
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-508405e7e0aa4f5fb410eac068efe138
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

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