Hydrochloric Acid → 1-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid

HRID 409451ノート

反応式

HRID 409451 の反応式
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[C:16]([N:18]3[CH2:22][C@@H:21]([N:23]([CH2:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=4)[C:24]4[N:29]=[CH:28][C:27]([C:30]5[CH:31]=[N:32][NH:33][CH:34]=5)=[CH:26][N:25]=4)[CH2:20][C@H:19]3[CH2:50][CH3:51])[C:15]([Cl:52])=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.[Li+].[OH-].Cl>CO>[F:49][C:46]([F:47])([F:48])[C:38]1[CH:37]=[C:36]([CH:41]=[C:40]([C:42]([F:43])([F:44])[F:45])[CH:39]=1)[CH2:35][N:23]([C:24]1[N:25]=[CH:26][C:27]([C:30]2[CH:34]=[N:33][NH:32][CH:31]=2)=[CH:28][N:29]=1)[C@@H:21]1[CH2:22][N:18]([C:16]2[C:15]([Cl:52])=[CH:14][N:13]=[C:12]([N:9]3[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]3)[N:17]=2)[C@H:19]([CH2:50][CH3:51])[CH2:20]1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 866483941-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid ethyl ester

生成物 1

HCID 596144111-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid収率 20%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A 15 ml round-bottom flask is charged with 1-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid ethyl ester, 2N LiOH (0.4 ml, 0.8 mmol) THF (0.5 ml) and MeOH (1 ml). The mixture is then stirred at rt for 1 hour. PH is adjusted to 6 using 1 N HCl and resulted solution is extracted with EtOAc. The organic layer is dried over Na2SO4 and removal of solvent, purification with reverse phase column give 1-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid (13 mg, 0.017 mmol, 20% for 3 steps).

後処理

  1. customresulted solution
  2. extractionis extracted with EtOAc
  3. dry with materialThe organic layer is dried over Na2SO4 and removal of solvent, purification with reverse phase column

出典と根拠

ORDレコード
ord-443e7d23d1ce43e1976866b181876d0d
出典データセット
uspto-grants-2014_06
特許番号
US08759365B2

反応ノート

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