2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one → 8-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 577509Notes

Reaction equation

HRID 577509 reaction equation
C([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:32])[C:20]([C:26]4[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=4)=[CH:21][CH:22]=3)[C:17]2=[O:33])=[C:13]([CH3:34])[CH:12]=[C:11]([CH3:35])[N:10]=1)C1C=CC=CC=1>C(O)(C(F)(F)F)=O>[Cl:32][C:19]1[C:20]([C:26]2[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=2)=[CH:21][CH:22]=[C:23]2[C:18]=1[C:17](=[O:33])[N:16]([CH2:15][C:14]1[C:9](=[O:8])[NH:10][C:11]([CH3:35])=[CH:12][C:13]=1[CH3:34])[CH2:25][CH2:24]2

Participants

3

Reactant 1

HCID 867237352-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867237368-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 17.8%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (66c, 60 mg, 0.12 mmol) in TFA (3 mL) was stirred at room temperature overnight. The reaction mixture was concentrated under vacuum and the residue purified by prep chromatography to give the title compound (Example 66, 8.5 mg, 17%) as a white solid. 1H NMR (700 MHz, DMSO-d6) δ 11.56 (br. s, 1H) 7.44 (d, J=7.70 Hz, 1H) 7.35 (d, J=7.70 Hz, 1H) 7.50 (d, J=1.76 Hz, 1H) 6.29 (d, J=1.76 Hz, 1H) 5.90 (s, 1H) 4.60 (s, 2H) 3.61 (s, 3H) 3.46-3.50 (m, 2H) 2.91 (t, J=5.83 Hz, 2H) 2.19 (s, 3H) 2.14 (s, 3H); MS 397.0 [M+1].

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue purified by prep chromatography

Sources & evidence

ORD record
ord-a9e332bf9a8d4608b33031a699f60a92
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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