Trifluoroacetic acid → 2-(2-(2-(2-((6-(Piperidin-4-yl)pyridin-3-yl)-amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1779008Notes

Reaction equation

HRID 1779008 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9](=[O:49])[CH2:10][C:11]1[CH:48]=[CH:47][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:27]=[CH:28][C:29]([CH:32]3[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]3)=[N:30][CH:31]=2)[N:16]=1>C(Cl)Cl>[NH:35]1[CH2:36][CH2:37][CH:32]([C:29]2[N:30]=[CH:31][C:26]([NH:25][C:17]3[N:16]=[C:15]([CH2:14][CH2:13][C:12]4[CH:45]=[CH:46][CH:47]=[CH:48][C:11]=4[CH2:10][C:9]([NH2:8])=[O:49])[C:20]([C:21]([F:23])([F:22])[F:24])=[CH:19][N:18]=3)=[CH:27][CH:28]=2)[CH2:33][CH2:34]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712663tert-Butyl 4-(5-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Product 1

HCID 730543142-(2-(2-(2-((6-(Piperidin-4-yl)pyridin-3-yl)-amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 85.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.5 mL) was added to a solution of tert-butyl 4-(5-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (A47) (58 mg, 0.099 mmol) in DCM (5 mL) and the resulting solution stirred for 18 hours at room temperature. The volatiles were evaporated under reduced pressure and the residue partitioned between 2 M aqueous NaOH (10 mL) and EtOAc (25 mL). The organic layer was separated and washed with water (25 mL), brine (25 mL), dried (Na2SO4) and concentrated under reduced pressure to give the title compound 13 as a white solid (41 mg, 85%); 1H NMR (400 MHz, d4-MeOH) δ 8.78 (d, J=2.1 Hz, 1H), 8.61 (d, J=0.6 Hz, 1H), 8.19 (dd, J=8.6, 2.6 Hz, 1H), 7.31 (d, J=8.5 Hz, 1H), 7.26 (d, J=6.3 Hz, 1H), 7.24-7.15 (m, 3H), 3.67 (s, 2H), 3.22-3.15 (m, 4H), 3.14-3.05 (m, 2H), 2.90-2.70 (m, 3H), 1.93 (d, J=13.9 Hz, 2H), 1.75 (m, 2H). LCMS-A: rt 4.552 min; m/z 485 [M+H]+.

Workup

  1. customThe volatiles were evaporated under reduced pressure
  2. customthe residue partitioned between 2 M aqueous NaOH (10 mL) and EtOAc (25 mL)
  3. customThe organic layer was separated
  4. washwashed with water (25 mL), brine (25 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cb78e7e82d1b4bd193b8d7e46c7473f8
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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