Methanol → 2-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1,2-dihydro-1-oxoisoquinolin-5-yl)acetamide

HRID 1037779Notes

Reaction equation

HRID 1037779 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[NH2:16][C:17]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:18]=1[CH:19]=[CH:20][N:21]([CH2:28][C:29]1[CH:30]=[N:31][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:33][CH:34]=1)[C:22]2=[O:27].C(N(CC)C(C)C)(C)C.CO>S(Cl)(Cl)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH:19]=[CH:20][N:21]([CH2:28][C:29]2[CH:30]=[N:31][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:33][CH:34]=2)[C:22]3=[O:27])=[O:11])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13]

Participants

6

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 35198824-Chloro-3-(trifluoromethyl)phenylacetic acidHCID 687691315-Amino-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)isoquinolin-1(2H)-one

Product 1

HCID 866476542-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1,2-dihydro-1-oxoisoquinolin-5-yl)acetamideYield 74.7%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
60 °C

Procedure

2-(4-Chloro-3-(trifluoromethyl)phenyl)acetic acid (142 mg, 0.000595 mol) was dissolved in thionyl chloride (10 mL) and the mixture was stirred at 60° C. for 3 hours. The volatiles were removed and the residue was dissolved in tetrahydrofuran. 5-Amino-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)isoquinolin-1(2H)-one (100.0 mg, 0.0002975 mol) and N,N-diisopropylethylamine (0.104 mL, 0.000595 mol) were added and the mixture was stirred for 1 hour at room temperature. Methanol was added to quench the reaction and the volatiles were removed. The residue was dissolved in ethylacetate, washed with water, sodium carbonate solution and brine and purified by column to obtain the product as a beige solid (120 mg). MS m/z=540.4(M+H).

Workup

  1. customThe volatiles were removed
  2. dissolutionthe residue was dissolved in tetrahydrofuran
  3. stirringthe mixture was stirred for 1 hour at room temperature
  4. customto quench
  5. customthe reaction
  6. customthe volatiles were removed
  7. dissolutionThe residue was dissolved in ethylacetate
  8. washwashed with water, sodium carbonate solution and brine
  9. custompurified by column

Sources & evidence

ORD record
ord-1f0bbc6391a14333bd445ec400b65c6e
Source dataset
uspto-grants-2013_10
Patent number
US08546579B2

Reaction notes

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