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

HRID 1779046Notes

Reaction equation

HRID 1779046 reaction equation
[NH2:1][C:2](=[O:40])[CH2:3][C:4]1[CH:39]=[CH:38][CH:37]=[CH:36][C:5]=1[CH2:6][CH2:7][C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26]3)=[CH:21][CH:20]=2)[N:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH:27]1[CH2:28][CH:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:10]3[N:9]=[C:8]([CH2:7][CH2:6][C:5]4[CH:36]=[CH:37][CH:38]=[CH:39][C:4]=4[CH2:3][C:2]([NH2:1])=[O:40])[C:13]([C:14]([F:16])([F:15])[F:17])=[CH:12][N:11]=3)=[CH:20][CH:21]=2)[CH2:26]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712689tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

Product 1

HCID 730548692-(2-(2-(2-((4-(Azetidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 99.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate (A82) (0.346 g, 0.623 mmol) and trifluoroacetic acid (1 mL) in DCM (10 mL) was stirred at room temperature for 22 hours. The volatiles were removed in vacuo and 2 M aqueous NaOH (15 mL) was added to the residue. Water (20 mL) was added and the resulting suspension sonicated for 2 minutes, filtered and the filter cake washed with water and dried to give the title compound 20 as a white solid (0.283 g, 99%); 1H NMR (300 MHz, d6-DMSO) δ 10.26 (s, 1H), 8.69 (s, 1H), 7.78 (d, J=8.6 Hz, 2H), 7.43 (s, 1H), 7.36 (d, J=8.6 Hz, 2H), 7.25-7.15 (m, 4H), 6.92 (s, 1H), 4.21 (brs, 2H), 4.06-3.99 (m, 3H), 3.50 (s, 2H), 3.12-3.05 (m, 5H). LCMS-B: rt 5.442 min; m/z 456 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo and 2 M aqueous NaOH (15 mL)
  2. additionwas added to the residue
  3. additionWater (20 mL) was added
  4. customthe resulting suspension sonicated for 2 minutes
  5. filtrationfiltered
  6. washthe filter cake washed with water
  7. customdried

Sources & evidence

ORD record
ord-1bd6a14e6b8d416b89d83c40124389bc
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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