Trifluoroacetic acid → 2-(5-Fluoro-2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1778994Notes

Reaction equation

HRID 1778994 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9](=[O:50])[CH2:10][C:11]1[CH:48]=[C:47]([F:49])[CH:46]=[CH:45][C:12]=1[CH2:13][CH2:14][C:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][N:18]=[C:17]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH:32]3[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]3)=[CH:28][CH:27]=2)[N:16]=1>C(Cl)Cl>[F:49][C:47]1[CH:46]=[CH:45][C:12]([CH2:13][CH2:14][C:15]2[C:20]([C:21]([F:23])([F:24])[F:22])=[CH:19][N:18]=[C:17]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([CH:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)=[CH:28][CH:27]=3)[N:16]=2)=[C:11]([CH2:10][C:9]([NH2:8])=[O:50])[CH:48]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712656HCID 86712656, compound

Product 1

HCID 730551532-(5-Fluoro-2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.825 mL, 10.8 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)-4-fluorophenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A37) (0.162 g, 0.269 mmol) in DCM (20 mL) under nitrogen and the resulting solution stirred for 24 hours at room temperature. 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 6 column volumes of 5% v/v aqueous ammonia in MeOH. The volatiles from the ammoniacal eluent were evaporated under reduced pressure to give the title compound 9 as a yellow solid (0.117 g, 87%); 1H NMR (400 MHz, d6-DMSO) δ 10.12 (s, 1H), 8.65 (s, 1H), 7.64 (d, J=8.6 Hz, 2H), 7.48 (s, 1H), 7.23-7.13 (m, 3H), 7.08 (dd, J=10.2, 2.8 Hz, 1H), 7.04-6.95 (m, 2H), 3.50 (s, 2H), 3.14-2.95 (m, 6H), 2.63-2.52 (m, 3H), 1.67 (d, J=10.8 Hz, 2H), 1.49 (qd, J=12.4, 3.9 Hz, 2H). LCMS-A: rt 4.853 min; m/z 502 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. washThe column was eluted with 5 column volumes of MeOH
  3. customThe volatiles from the ammoniacal eluent were evaporated under reduced pressure

Sources & evidence

ORD record
ord-b2e5502e175849b287c45adf80d65597
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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