2-Chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine → 2-N-(6,6-dimethyl-4,7-dihydropyrazolo[5,1-c][1,4]oxazin-3-yl)-4-N-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine

HRID 1503479Notes

Reaction equation

HRID 1503479 reaction equation
[CH3:1][C:2]1([CH3:12])[O:7][CH2:6][C:5]2=[C:8]([NH2:11])[CH:9]=[N:10][N:4]2[CH2:3]1.Cl[C:14]1[N:19]=[C:18]([NH:20][CH3:21])[C:17]([C:22]([F:25])([F:24])[F:23])=[CH:16][N:15]=1>CC(O)(C)C>[CH3:1][C:2]1([CH3:12])[O:7][CH2:6][C:5]2=[C:8]([NH:11][C:14]3[N:19]=[C:18]([NH:20][CH3:21])[C:17]([C:22]([F:25])([F:23])[F:24])=[CH:16][N:15]=3)[CH:9]=[N:10][N:4]2[CH2:3]1

Participants

4

Reactant 2

HCID 210775872-Chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amineHCID 900104216,6-dimethyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-3-amine

Product 1

HCID 722014892-N-(6,6-dimethyl-4,7-dihydropyrazolo[5,1-c][1,4]oxazin-3-yl)-4-N-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamineYield 36%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial equipped with a magnetic stirrer was charged with 6,6-dimethyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-3-amine (13 mg, 0.078 mmol), 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (20 mg, 0.095 mmol), and t-BuOH (0.5 mL). The mixture was heated at 100° C. under microwave irradiation for 15 min. After concentration, the residue was purified by prep-HPLC to give the title compound (9.5 mg, 36%). 1H NMR (500 MHz, CDCl3) δ 8.09 (s, 1H), 7.67 (s, 1H), 6.79 (s, 1H), 5.18 (s, 1H), 4.83 (s, 2H), 3.93 (s, 2H), 3.00 (d, J=4.5 Hz, 3H), 1.63 (s, 6H). LC-MS (Method B): m/z=343.3 (M+H)+, 4.77 min, 98.2% purity.

Workup

  1. customA microwave vial equipped with a magnetic stirrer
  2. concentrationAfter concentration
  3. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-61752ca0b37e49aca396469ac48d660d
Source dataset
uspto-grants-2015_12
Patent number
US09212186B2

Reaction notes

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