Trifluoroacetic acid → 8-chloro-7-(difluoromethoxy)-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one

HRID 577479Notes

Reaction equation

HRID 577479 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:30])[C:20]([O:26][CH:27]([F:29])[F:28])=[CH:21][CH:22]=3)[C:17]2=[O:31])=[C:13]([CH3:32])[CH:12]=[C:11]([CH3:33])[N:10]=1)C1C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:30][C:19]1[C:20]([O:26][CH:27]([F:29])[F:28])=[CH:21][CH:22]=[C:23]2[C:18]=1[C:17](=[O:31])[N:16]([CH2:15][C:14]1[C:9](=[O:8])[NH:10][C:11]([CH3:33])=[CH:12][C:13]=1[CH3:32])[CH2:25][CH2:24]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 867237052-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-(difluoromethoxy)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 783193628-chloro-7-(difluoromethoxy)-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-oneYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-(difluoromethoxy)-3,4-dihydroisoquinolin-1(2H)-one (1i, 0.08 g, 0.169 mmol) in CH2Cl2 (10 mL) was added TFA (10 mL) at room temperature. The resulting mixture was stirred at room temperature for 4 hours. The mixture was concentrated under vacuum to give a residue, which was dissolved in CH2Cl2 (20 mL) and then washed with sat. NaHCO3 (5 mL), brine (5 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by prep. TLC (EtOAc) to obtain the title compound (Example 1, 43.1 mg, 67%) as a white solid. 1H NMR (400 MHz, methanol-d4) δ 7.36-7.34 (m, 1H), 7.24-7.22 (m, 1H), 7.00-6.63 (m, 1H), 6.11 (s, 1H), 4.76 (s, 2H), 3.51-3.48 (m, 2H), 2.90-2.87 (m, 2H), 2.29 (s, 3H), 2.25 (s, 3H); MS 382.9 [M+1].

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. customto give a residue, which
  3. washwashed with sat. NaHCO3 (5 mL), brine (5 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by prep

Sources & evidence

ORD record
ord-b088e31ce33348bd84b3a218bc81297b
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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