Water → HCID 58102796, compound

HRID 450162Notes

Reaction equation

HRID 450162 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][N:5]([CH3:7])[CH:6]=1.Cl[C:9]1[N:14]=[C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:12]=[C:11]([N:21]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[N:23]=[C:22]2[CH:30]([F:32])[F:31])[N:10]=1.O>CS(C)=O>[F:32][CH:30]([F:31])[C:22]1[N:21]([C:11]2[N:12]=[C:13]([N:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)[N:14]=[C:9]([NH:1][C:2]3[CH:3]=[N:4][N:5]([CH3:7])[CH:6]=3)[N:10]=2)[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]=1

Participants

5

Reactant 3

HCID 962WaterHCID 47709901-methyl-1H-pyrazol-4-amineHCID 220368724-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-yl)morpholine

Product 1

HCID 58102796HCID 58102796, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 0.405 g (4.27 mmol) of 4-amino-1-methylpyrazole and 0.695 g (1.90 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in DMSO (5 mL) was heated at 125° C. for 15 min. The reaction mixture was cooled to room temperature and water was added. The solid was collected by filtration, washed with water, and dried. Chromatography on alumina, eluting with hexanes/EtOAc (1:1) gave a brown powder. Recrystallization from ethanol/CH2Cl2 gave 0.145 g (18% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(1-methyl-1H-pyrazol-4-yl)-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 225-226° C.; 1H NMR (DMSO-d6) (rotamers) δ 10.00 (s, 1H), 9.73 (s, 0.2H), 8.60 (d, J=8.0 Hz, 1H), 8.29 (d, J=7.6 Hz, 0.2H), 7.92 (t, JHF=52.8 Hz, 1H), 7.86-7.80 (m, 2.6H), 7.68 (t, JHF=52.6 Hz, 0.2H), 7.59 (s, 1H), 7.52-7.42 (m, 2.9H), 3.85-3.82 (m, 8.4H), 3.75-3.73 (m, 4.8H); Anal. Calcd. for C19H19F2N9O 0.06EtOAc 0.24H2O: C, 52.9; H, 4.6; N, 28.8. Found: C, 52.9; H, 4.5; N, 28.6%.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe solid was collected by filtration
  3. washwashed with water
  4. customdried
  5. washChromatography on alumina, eluting with hexanes/EtOAc (1:1)
  6. customgave a brown powder
  7. customRecrystallization from ethanol/CH2Cl2

Sources & evidence

ORD record
ord-4ac8b142dfdf4d5bb511db4facbf0f3e
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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