2-Chloropyrimidine → {1-[6-(3,4-Difluoro-phenoxy)-4-pyrimidin-2-yl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid benzyl ester

HRID 1965174Notes

Reaction equation

HRID 1965174 reaction equation
[CH2:1]([O:8][C:9](=[O:35])[NH:10][CH:11]([C:16]([N:18]1[CH2:22][CH2:21][CH:20]2[NH:23][CH2:24][CH:25]([O:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[C:29]([F:34])[CH:28]=3)[CH:19]12)=[O:17])[C:12]([CH3:15])([CH3:14])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[C:46]1[N:51]=[CH:50][CH:49]=[CH:48][N:47]=1>CN(C=O)C.O>[CH2:1]([O:8][C:9](=[O:35])[NH:10][CH:11]([C:16]([N:18]1[CH2:22][CH2:21][CH:20]2[N:23]([C:46]3[N:51]=[CH:50][CH:49]=[CH:48][N:47]=3)[CH2:24][CH:25]([O:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[C:29]([F:34])[CH:28]=3)[CH:19]12)=[O:17])[C:12]([CH3:15])([CH3:14])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 744042-ChloropyrimidineHCID 81531DiisopropylethylamineHCID 67608719{1-[6-(3,4-Difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid benzyl ester

Product 1

HCID 67608380{1-[6-(3,4-Difluoro-phenoxy)-4-pyrimidin-2-yl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid benzyl esterYield 60.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Secondary amine 24 (200 mg, 0.41 mmol), DIPEA (110 μL, 0.62 mmol), and 2-chloro-pyrimidine (62 mg, 0.53 mmol) were dissolved in DMF (4 mL) and stirred at 80° C. After 12 h, the reaction mixture was cooled to ambient temperature, diluted with water, and extracted with EtOAc. The combined organic extracts were washed with brine and dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (1:1 hexanes/EtOAc) to afford 140 mg (60%) of 29 as a colorless oil. Mass spectrum, m/z [566.0] (M+H)+.

Workup

  1. temperaturethe reaction mixture was cooled to ambient temperature
  2. extractionextracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash silica gel chromatography (1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-4623be0b93be434fbfa51c621fc93e9b
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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