Trifluoroacetic acid → Methyl 4-(4-fluorophenyl)-6-methyl-2-oxo-3-[({4-oxo-4-[3-(4-piperidinyl)anilino]butyl}amino)carbonyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

HRID 1452659Notes

Reaction equation

HRID 1452659 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[C:16]([CH:45]=[CH:46][CH:47]=2)[NH:17][C:18](=[O:44])[CH2:19][CH2:20][CH2:21][NH:22][C:23]([N:25]2[CH:30]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[C:29]([C:38]([O:40][CH3:41])=[O:39])=[C:28]([CH3:42])[NH:27][C:26]2=[O:43])=[O:24])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:37][C:34]1[CH:35]=[CH:36][C:31]([CH:30]2[C:29]([C:38]([O:40][CH3:41])=[O:39])=[C:28]([CH3:42])[NH:27][C:26](=[O:43])[N:25]2[C:23]([NH:22][CH2:21][CH2:20][CH2:19][C:18](=[O:44])[NH:17][C:16]2[CH:45]=[CH:46][CH:47]=[C:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH:15]=2)=[O:24])=[CH:32][CH:33]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57526947Methyl 3-{[(4-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]anilino}-4-oxobutyl)amino]carbonyl}-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

Product 1

HCID 57526933Methyl 4-(4-fluorophenyl)-6-methyl-2-oxo-3-[({4-oxo-4-[3-(4-piperidinyl)anilino]butyl}amino)carbonyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylateYield 99.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a solution of methyl 3-{[(4-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]anilino}-4-oxobutyl)amino]carbonyl}-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate (40.9 mg, 0.0628 mmol) in dichloromethane (2.00 mL) at 0° C. was slowly added trifluoroacetic acid (71.6 mg, 0.628 mmol). The reaction mixture was stirred at room temperature for 10 min and concentrated in vacuo. The residue was dissolved in iso-PrOH/CHCl3 (1:3, 10 mL) and basified to pH 11 with 10% KOH solution, washed with H2O, followed by brine. The organic layer was dried over MgSO4 and concentrated in vacuo to afford the desired product (34.6 mg, 99%): 1H NMR (400 MHz, CDCl3) δ 8.00 (m, 3H), 7.67 (s, 1H), 7.35-7.27 (m, 4H), 7.04-6.98 (m, 3H), 6.65 (s, 1H), 3.72 (s, 3H), 3.5-3.48 (m, 2H), 3.20-3.11 (m, 3H), 2.42 (t, 2H, J=7.5 Hz), 2.36 (s, 3H), 2.13-2.06 (m, 2H), 1.97-1.88 (m, 4H); ESMS m/e: 552.3 (M+H)+.

Workup

  1. customat 0° C.
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in iso-PrOH/CHCl3 (1:3, 10 mL)
  4. washwashed with H2O
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c40f107a7e3e427f84494db323f93f32
Source dataset
uspto-grants-2009_01
Patent number
US07473698B2

Reaction notes

Loading…