Trifluoroacetic acid → 4-{5-[3-methyl-5-({4-[(3R)-pyrrolidin-3-yloxy]-pyrimidin-2-yl}amino)phenyl]-1,3-thiazol-2-yl}-1,4-diazepan-2-one

HRID 1028129Notes

Reaction equation

HRID 1028129 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:21][C:22]2[N:27]=[C:26]([O:28][C@@H:29]3[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]3)[CH:25]=[CH:24][N:23]=2)[CH:5]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:19][CH2:18][CH2:17][NH:16][C:15](=[O:20])[CH2:14]3)=[N:10][CH:9]=2)[CH:7]=1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:19][CH2:18][CH2:17][NH:16][C:15](=[O:20])[CH2:14]3)=[N:10][CH:9]=2)[CH:5]=[C:4]([NH:21][C:22]2[N:27]=[C:26]([O:28][C@@H:29]3[CH2:33][CH2:32][NH:31][CH2:30]3)[CH:25]=[CH:24][N:23]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86674326tert-Butyl (3R)-3-{[2-({3-methyl-5-[2-(3-oxo-1,4-diazepan-1-yl)-1,3-thiazol-5-yl]-phenyl}amino)pyrimidin-4-yl]oxy}pyrrolidine-1-carboxylate

Product 1

HCID 710753594-{5-[3-methyl-5-({4-[(3R)-pyrrolidin-3-yloxy]-pyrimidin-2-yl}amino)phenyl]-1,3-thiazol-2-yl}-1,4-diazepan-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (3R)-3-{[2-({3-methyl-5-[2-(3-oxo-1,4-diazepan-1-yl)-1,3-thiazol-5-yl]-phenyl}amino)pyrimidin-4-yl]oxy}pyrrolidine-1-carboxylate (80 mg, 0.14 mmol) was taken up in dichloromethane (1 mL). The mixture was treated with trifluoroacetic acid (0.2 mL, 2.6 mmol) and left to stir for 1 hour. The reaction was neutralized with saturated aqueous sodium bicarbonate, and extracted with ethyl acetate (×3). The combined organics were washed with brine, dried over sodium sulfate, concentrated, and purified by Combiflash (methanol/dichloromethane) to provide 4-{5-[3-methyl-5-({4-[(3R)-pyrrolidin-3-yloxy]-pyrimidin-2-yl}amino)phenyl]-1,3-thiazol-2-yl}-1,4-diazepan-2-one. MS APCI: [M+H]+ m/z 466.1. 1H NMR (500 MHz, DMSO-d6) δ 9.53 (s, 1H), 8.22 (d, J=5.6, 1H), 7.63 (m, 2H), 7.49 (s, 1H), 7.38 (s, 1H), 6.96 (s, 1H), 6.25 (d, J=5.6, 1H), 5.56 (s, 1H), 4.16 (s, 2H), 4.10 (s, 1H), 3.80 (s, 2H), 3.44-3.05 (m, 5H), 2.27 (s, 3H), 2.21 (m, 1H), 2.06 (m, 1H), 1.77 (m, 2H). rhSyk=+++

Workup

  1. waitleft
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by Combiflash (methanol/dichloromethane)

Sources & evidence

ORD record
ord-2741002ed81d45f1901f4c3106a32296
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

Loading…