Diethyl Ether → 1,1-Dimethylethyl N-[[4-[[4-chloro-5-(trifluoromethyl)-2-pyrimidinyl]amino]phenyl]methyl]carbamate

HRID 1778967Notes

Reaction equation

HRID 1778967 reaction equation
CCOCC.Cl[C:7]1[N:12]=[C:11]([Cl:13])[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=1.[NH2:18][C:19]1[CH:33]=[CH:32][C:22]([CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:21][CH:20]=1.CCN(CC)CC>[Cl-].[Cl-].[Zn+2].ClCCCl.CC(O)(C)C>[Cl:13][C:11]1[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=[C:7]([NH:18][C:19]2[CH:33]=[CH:32][C:22]([CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[CH:21][CH:20]=2)[N:12]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 2756041tert-butyl N-[(4-aminophenyl)methyl]carbamateHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidine

Product 1

HCID 575846421,1-Dimethylethyl N-[[4-[[4-chloro-5-(trifluoromethyl)-2-pyrimidinyl]amino]phenyl]methyl]carbamate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolventHCID 6386tert-ButanolSolvent

Procedure

A 1.0 M ZnCl2 solution in Et2O (5.40 mL, 5.40 mmol) was added cautiously to a stirred suspension of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (1.03 g, 4.72 mmol) in 1:1 t-BuOH:DCE (200 mL) at room temperature. After stirring for 20 minutes, tert-butyl 4-aminobenzylcarbamate (A11) (1.00 g, 4.50 mmol) was added followed by Et3N (752 μL, 5.40 mmol) and the resulting mixture stirred at room temperature overnight. The volatiles were removed in vacuo and the resulting tan solid was suspended in water (500 mL). The suspension was sonicated for 10 minutes, filtered and the filter cake was washed with water (2×100 mL) then dried under high vacuum to give the title compound A12 as a tan solid (1.77 g, 97%); 1H NMR (400 MHz, d6-DMSO) δ 10.63 (s, 1H), 8.79 (s, 1H), 7.61 (d, J=8.1 Hz, 2H), 7.36 (t, J=7.6 Hz, 1H), 7.22 (d, J=8.4 Hz, 2H), 4.10 (d, J=6.0 Hz, 2H), 1.40 (s, 9H). LCMS-A: rt 6.356 min; m/z 401 [M−1]−.

Workup

  1. customat room temperature
  2. stirringthe resulting mixture stirred at room temperature overnight
  3. customThe volatiles were removed in vacuo
  4. customThe suspension was sonicated for 10 minutes
  5. filtrationfiltered
  6. washthe filter cake was washed with water (2×100 mL)
  7. customthen dried under high vacuum

Sources & evidence

ORD record
ord-d5c7911654b24682bf1d77b11e1d23c5
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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