Diisopropylethylamine → HCID 117697825, compound

HRID 1778459Notes

Reaction equation

HRID 1778459 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:12][CH:11]2[NH:13][CH:7]([CH2:8][O:9][CH2:10]2)[CH2:6]1)=[O:4].[CH3:14][O:15][C:16]([C:18]1[C@H:19]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=2[Cl:38])[N:20]=[C:21]([C:26]2[S:27][CH:28]=[CH:29][N:30]=2)[NH:22][C:23]=1[CH2:24]Br)=[O:17].CCN(C(C)C)C(C)C>C(Cl)CCl.CCOC(C)=O>[Cl:38][C:32]1[CH:33]=[C:34]([F:37])[CH:35]=[CH:36][C:31]=1[C@H:19]1[C:18]([C:16]([O:15][CH3:14])=[O:17])=[C:23]([CH2:24][N:13]2[CH:7]3[CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:12][CH:11]2[CH2:10][O:9][CH2:8]3)[NH:22][C:21]([C:26]2[S:27][CH:28]=[CH:29][N:30]=2)=[N:20]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 89995948Methyl (R)-6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylateHCID 91634089HCID 91634089, compound

Product 1

HCID 117697825HCID 117697825, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution 3-oxa-9-azabicyclo[3.3.1]nonane-7-carboxylic acid methyl ester (90 mg, 0.48 mmol) (PharmaBlock (Nanjing) R&D Co. Ltd, CAS: 1363382-76-6) and (R)-6-bromomethyl-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (104 mg, 0.24 mmol) in ClCH2CH2Cl (5 mL) was added DIPEA (0.15 mL, 0.48 mmol) at room temperature. The reaction mixture was stirred overnight at room temperature, then diluted with EtOAc (60 mL), washed with sat. NH4Cl, sat. NaHCO3 and brine (20 mL) respectively. The organic layer was dried over Na2SO4, concentrated under reduced pressure to give methyl 9-[[(4R)-4-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]-3-oxa-9-azabicyclo[3.3.1]nonane-7-carboxylate as a crude product which was used directly in next step.

Workup

  1. washwashed 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

Sources & evidence

ORD record
ord-c13d6bdbc285419784663402bfb80b29
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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