Potassium Carbonate → (3R)-tert-Butyl 4-((6-(5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-3-methylpiperazine-1-carboxylate

HRID 906474Notes

Reaction equation

HRID 906474 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[C:9]([F:52])[C:10]([CH3:51])=[C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[C:19](=[O:23])[N:18]([CH2:24][C:25]([CH3:35])([CH3:34])[CH2:26][O:27]C(=O)C(C)(C)C)[CH:17]=[C:16]4[CH2:36][N:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][C@H:38]3[CH3:50])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+]>CO.O>[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[C:9]([F:52])[C:10]([CH3:51])=[C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[C:19](=[O:23])[N:18]([CH2:24][C:25]([CH3:34])([CH3:35])[CH2:26][OH:27])[CH:17]=[C:16]4[CH2:36][N:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][C@H:38]3[CH3:50])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 86640984(3R)-tert-Butyl 4-((6-(5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)-2-(2,2-dimethyl-3-(pivaloyloxy)propyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-3-methylpiperazine-1-carboxylate

Product 1

HCID 67391573(3R)-tert-Butyl 4-((6-(5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-3-methylpiperazine-1-carboxylateYield 72.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
67 °C

Procedure

(3R)-tert-Butyl 4-((6-(5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)-2-(2,2-dimethyl-3-(pivaloyloxy)propyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-3-methylpiperazine-1-carboxylate (50.8 g) was dissolved in methanol (600 mL) and a solution of potassium carbonate (29.3 g) in water (100 mL) was added. The reaction was heated at reflux (internal temperature 67° C.) for 16 h. After cooling to 50° C., further water was slowly added until the mixture became opaque and the mixture was cooled to 23° C. over 1 h. The precipitate was collected by filtration, washed with water (100 mL) and isohexane (100 mL) and dried in vacuo at 45° C. to give the subtitle product (32.4 g).

Workup

  1. temperatureThe reaction was heated
  2. temperatureAfter cooling to 50° C.
  3. temperaturethe mixture was cooled to 23° C. over 1 h
  4. filtrationThe precipitate was collected by filtration
  5. washwashed with water (100 mL) and isohexane (100 mL)
  6. customdried in vacuo at 45° C.

Sources & evidence

ORD record
ord-16e81cc12b8b4e2b97fc22d91489f290
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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