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

HRID 1779079Notes

Reaction equation

HRID 1779079 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9](=[O:47])[CH2:10][C:11]1[CH:46]=[CH:45][CH:44]=[CH:43][C:12]=1[CH2:13][CH2:14][C:15]1[C:20]([CH3:21])=[CH:19][N:18]=[C:17]([NH:22][C:23]2[CH:42]=[CH:41][C:26]([O:27][CH:28]3[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]3)=[CH:25][CH:24]=2)[N:16]=1>C(Cl)Cl>[CH3:21][C:20]1[C:15]([CH2:14][CH2:13][C:12]2[CH:43]=[CH:44][CH:45]=[CH:46][C:11]=2[CH2:10][C:9]([NH2:8])=[O:47])=[N:16][C:17]([NH:22][C:23]2[CH:42]=[CH:41][C:26]([O:27][CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[CH:25][CH:24]=2)=[N:18][CH:19]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712716tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenoxy)piperidine-1-carboxylate

Product 1

HCID 730557462-(2-(2-(5-Methyl-2-((4-(piperidin-4-yloxy)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.5 mL) was added to a cooled (water/ice bath 6° C.) solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenoxy)piperidine-1-carboxylate (A113) (0.050 g, 0.092 mmol) in DCM (2 mL) and the resulting mixture was stirred at room temperature for 4 hours. The volatiles were removed in vacuo then 2 M aqueous K2CO3 solution (10 mL) and water (10 mL) were added to the residue. The resulting suspension was sonicated for 1 minute, filtered and the filter cake dried to give the title compound 26 as a light pink solid (0.034 g, 83%); 1H NMR (300 MHz, d6-DMSO) δ 9.17 (s, 1H), 8.12 (s, 1H), 7.62 (d, J=8.9 Hz, 2H), 7.43 (s, 1H), 7.12-7.27 (m, 4H), 6.93 (s, 1H), 6.84 (d, J=8.9 Hz, 2H), 4.23-4.29 (m, 1H), 3.49 (s, 2H), 3.30-3.34 (m, 2H), 2.83-3.05 (m, 7H), 2.05 (s, 3H), 1.86-1.90 (m, 2H), 1.39-1.42 (m, 2H). LCMS-B: rt 4.717 min; m/z 446 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. addition2 M aqueous K2CO3 solution (10 mL) and water (10 mL) were added to the residue
  3. customThe resulting suspension was sonicated for 1 minute
  4. filtrationfiltered
  5. customthe filter cake dried

Sources & evidence

ORD record
ord-590f8f2f22f14e619cbde0f7949f2683
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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