Trifluoroacetic acid → HCID 117700192, compound

HRID 1778479Notes

Reaction equation

HRID 1778479 reaction equation
C(O[C:6](=[O:17])[NH:7][CH:8]1[CH2:15][CH:14]2[NH:16][CH:10]([CH2:11][O:12][CH2:13]2)[CH2:9]1)(C)(C)C.[CH3:18][O:19][C:20]([C:22]1[C@H:23]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[Cl:42])[N:24]=[C:25]([C:30]2[S:31][CH:32]=[CH:33][N:34]=2)[NH:26][C:27]=1[CH2:28]Br)=[O:21].[CH3:43]CN(C(C)C)C(C)C.FC(F)(F)C(O)=O>C(Cl)Cl.CCOC(C)=O>[CH3:18][O:19][C:20]([C:22]1[C@H:23]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[Cl:42])[N:24]=[C:25]([C:30]2[S:31][CH:32]=[CH:33][N:34]=2)[NH:26][C:27]=1[CH2:28][N:16]1[CH:14]2[CH2:15][CH:8]([NH:7][C:6](=[O:17])[CH3:43])[CH2:9][CH:10]1[CH2:11][O:12][CH2:13]2)=[O:21]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 69210205HCID 69210205, compoundHCID 89995948Methyl (R)-6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

Product 1

HCID 117700192HCID 117700192, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To the solution of (3-oxa-9-aza-bicyclo[3.3.1]non-7-yl)-carbamic acid tert-butyl ester (PharmaBlock (Nanjing) R&D Co. Ltd, catalog number: PB05636) (106 mg, 0.44 mmol) and Compound C (100 mg, 0.22 mmol) in CH2Cl2 (5 mL) was added DIPEA (0.14 mL, 0.44 mmol) at room temperature. The reaction mixture was stirred overnight at room temperature, then diluted with EtOAc (60 mL). The organic layer was washed with sat. NH4Cl, sat. NaHCO3 and brine (20 mL) respectively. The organic layer was dried over Na2SO4, and then concentrated under reduced pressure to give the crude product which was dissolved in CH2Cl2 (5 mL). To the solution was added trifluoroacetic acid (2 mL) at 0° C. The mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure to give the crude (R)-6-(7-amino-3-oxa-9-aza-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 AP) which was directly used for next step.

Workup

  1. washThe organic layer was washed with sat. NH4Cl, sat. NaHCO3 and brine (20 mL) respectively
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product which
  5. stirringThe mixture was stirred at room temperature for 2 hours
  6. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-1443ce117b104dc9833aa6a58c1b14ca
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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