Trifluoroacetic acid → (R)-6-(7-acetyl-3-oxa-7,9-diaza-bicyclo[3.3.1]non-9-ylmethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester

HRID 1778471Notes

Reaction equation

HRID 1778471 reaction equation
C([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16]([CH2:17][C:18]3[NH:19][C:20]([C:36]4[S:37][CH:38]=[CH:39][N:40]=4)=[N:21][C@@H:22]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=4[Cl:35])[C:23]=3[C:24]([O:26][CH3:27])=[O:25])[CH:10]([CH2:11][O:12][CH2:13]2)[CH2:9]1)=O)(C)(C)C.[C:41](O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:27][O:26][C:24]([C:23]1[C@H:22]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[Cl:35])[N:21]=[C:20]([C:36]2[S:37][CH:38]=[CH:39][N:40]=2)[NH:19][C:18]=1[CH2:17][N:16]1[CH:14]2[CH2:15][N:8]([C:6](=[O:5])[CH3:41])[CH2:9][CH:10]1[CH2:11][O:12][CH2:13]2)=[O:25]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 1176974139-[(R)-6-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-3,6-dihydro-pyrimidin-4-ylmethyl]-3-oxa-7,9-diaza-bicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl ester

Product 1

HCID 86293080(R)-6-(7-acetyl-3-oxa-7,9-diaza-bicyclo[3.3.1]non-9-ylmethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 9-[(R)-6-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-3,6-dihydro-pyrimidin-4-ylmethyl]-3-oxa-7,9-diaza-bicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl ester (280 mg, 0.47 mmol) in CH2Cl2 (10 mL) was added TFA (2 mL) dropwise in ice-bath. The mixture was stirred at room temperature for 16 hours. The mixture was neutralized with a saturated aqueous sodium bicarbonate solution and then extracted with CH2Cl2 (20 mL×2). The organic layer was washed with saturated aqueous sodium bicarbonate solution (20 mL×2), and then dried over anhydrous sodium sulfate and then concentrated in vacuo to afford (R)-6-(7-acetyl-3-oxa-7,9-diaza-bicyclo[3.3.1]non-9-ylmethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (Compound AC) as light yellow oil (230 mg, 98%) which was used for next step without further purification. MS: calc'd (MH+) 492, measured (MH+) 492.

Workup

  1. extractionextracted with CH2Cl2 (20 mL×2)
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution (20 mL×2)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f2a32d59f30e46f394ca0fbb37d6062c
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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