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

HRID 592371Notes

Reaction equation

HRID 592371 reaction equation
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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-cc35537c703d46b5a72558c41a0b2cb6
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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