Diisopropylethylamine → (R)-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

HRID 63675

反応式

HRID 63675 の反応式
[CH3:1][O:2][C:3]([C:5]1[C@H: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[C@H: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]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 152161024,4-DifluoroprolineHCID 89995948Methyl (R)-6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

生成物 1

HCID 73331268(R)-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

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of (R)-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 (R)-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 2) as a light yellow solid.

後処理

  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

出典と根拠

ORDレコード
ord-7a5aafacb02d44f3a0a493ceec3e2e58
出典データセット
uspto-grants-2016_09
特許番号
US09447086B2

関連ノート

読み込み中…