Diisopropylethylamine → HCID 73331267, compound

HRID 63673

Reaction equation

HRID 63673 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[Cl:25])[N:7]=[C:8]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)[NH:9][C:10]=1[CH2:11]Br)=[O:4].[F:26][C:27]1([F:35])[CH2:31][NH:30][C@H:29]([C:32]([OH:34])=[O:33])[CH2:28]1.CCN(C(C)C)C(C)C>ClCCCl.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[CH:6]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[Cl:25])[N:7]=[C:8]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)[NH:9][C:10]=1[CH2:11][N:30]1[CH2:31][C:27]([F:35])([F:26])[CH2:28][C@H:29]1[C:32]([OH:34])=[O:33])=[O:4]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 152161024,4-DifluoroprolineHCID 899959636-Bromomethyl-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester

Product 1

HCID 73331267HCID 73331267, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 6-bromomethyl-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (0.049 g, 0.11 mmol) and (S)-4,4-difluoro-pyrrolidine-2-carboxylic acid (0.044 g, 0.17 mmol) in 1,2-dichloroethane (5 mL) was added dropwise DIPEA (0.078 mL, 0.45 mmol). The reaction mixture was stirred at room temperature until the disappearance of starting material which was checked by LC/MS. The mixture was diluted with EtOAc (50 mL) and washed successively with saturated aqueous NH4Cl solution and brine. The organic layer was separated and dried over Na2SO4. The solvent was concentrated in vacuo and the crude product was purified by prep-HPLC to give 6-((S)-2-carboxy-4,4-difluoro-pyrrolidin-1-ylmethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (Example 1).

Workup

  1. washwashed successively with saturated aqueous NH4Cl solution and brine
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. concentrationThe solvent was concentrated in vacuo
  5. customthe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-b58e6cfc871c421eb871900673d052a7
Source dataset
uspto-grants-2016_09
Patent number
US09447086B2

Linked notes

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