反応 #679553

反応方程式

TFA

tert-butyl 3-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

tert-Butyl 3-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

→

title compound 4

収率 90.0%

1-(2-(2-(2-((4-(azetidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

収率 90.0%

溶媒

DCM

反応条件

後処理

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

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]+.

出典