Trifluoroacetic acid → 1-(2-(2-(2-((4-(Azetidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592371ノート

反応式

HRID 592371 の反応式
C(O)(C(F)(F)F)=O.[C:8]([C:11]1([C:14]2[CH:49]=[CH:48][CH:47]=[CH:46][C:15]=2[CH2:16][CH2:17][C:18]2[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][N:21]=[C:20]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([CH:35]4[CH2:38][N:37](C(OC(C)(C)C)=O)[CH2:36]4)=[CH:31][CH:30]=3)[N:19]=2)[CH2:13][CH2:12]1)(=[O:10])[NH2:9]>C(Cl)Cl>[NH:37]1[CH2:38][CH:35]([C:32]2[CH:33]=[CH:34][C:29]([NH:28][C:20]3[N:19]=[C:18]([CH2:17][CH2:16][C:15]4[CH:46]=[CH:47][CH:48]=[CH:49][C:14]=4[C:11]4([C:8]([NH2:9])=[O:10])[CH2:12][CH2:13]4)[C:23]([C:24]([F:26])([F:25])[F:27])=[CH:22][N:21]=3)=[CH:30][CH:31]=2)[CH2:36]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 86712290tert-Butyl 3-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

生成物 1

HCID 732964271-(2-(2-(2-((4-(Azetidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide収率 90%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of TFA (0.916 mL, 12.0 mmol) and tert-butyl 3-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate (A9) (174 mg, 0.299 mmol) in DCM (10 mL) was stirred for 16 hours at room temperature under nitrogen. The volatiles were removed in vacuo and the residue was taken up in MeOH and loaded onto an SCX cartridge (10 g). The column was eluted with 5 column volumes of MeOH and then 5 column volumes of 5% v/v aqueous ammonia in MeOH to elute the amine product. The ammoniacal filtrate was evaporated under reduced pressure and dried under high vacuum to give the title compound 4 as a yellow solid (129 mg, 90%); 1H NMR (400 MHz, d6-DMSO) δ 10.19 (s, 1H), 8.68 (s, 1H), 7.77-7.67 (m, 2H), 7.38-7.26 (m, 5H), 7.26-7.18 (m, 1H), 6.99 (s, 1H), 6.00 (s, 2H), 3.86 (s, 3H), 3.71 (s, 2H), 3.22-3.13 (m, 2H), 3.13-3.05 (m, 2H), 1.44 (s, 2H), 0.96 (s, 2H). LCMS-A: rt 4.591 min; m/z 482 [M+H]+.

後処理

  1. customThe volatiles were removed in vacuo
  2. washThe column was eluted with 5 column volumes of MeOH
  3. wash5 column volumes of 5% v/v aqueous ammonia in MeOH to elute the amine product
  4. customThe ammoniacal filtrate was evaporated under reduced pressure
  5. customdried under high vacuum

出典と根拠

ORDレコード
ord-cc35537c703d46b5a72558c41a0b2cb6
出典データセット
uspto-grants-2016_01
特許番号
US09238644B2

反応ノート

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