1H-Pyrazol-3-amine, 5-methyl- → 2,6-dichloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine

HRID 415442Notes

Reaction equation

HRID 415442 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([F:9])=[C:4](Cl)[N:3]=1.[CH3:11][C:12]1[NH:16][N:15]=[C:14]([NH2:17])[CH:13]=1>C(O)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:17][C:14]2[CH:13]=[C:12]([CH3:11])[NH:16][N:15]=2)[C:5]([F:9])=[C:6]([Cl:8])[N:7]=1

Participants

4

Reactant 2

HCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 133889932,4,6-Trichloro-5-fluoropyrimidine

Product 1

HCID 509937272,6-dichloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amineYield 70.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2,4,6-trichloro-5-fluoropyrimidine (4.03 g) in absolute ethanol (100 mL) was added DIEPA (5.3 mL) and 5-methyl-1H-pyrazol-3-amine (2.03 g). The resulting solution was stirred at room temperature for 6 hours. The precipitation was filtered and washed with cold ethanol. The compound was dried by vacuum oven give 2,6-dichloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine as solid (3.7 g). m/z 262. A mixture of morpholine (0.181 mL), 2,6-dichloro-5-fluoro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (500 mg) and DIPEA (0.505 ml) in absolute ethanol (10.0 ml) was heated at 80° C. for 5 hours. The solvent was removed under reduced pressure and the residue was purified by Gilson (10-50% MeCN/H2O, 15 minutes) to give the titled compound as solid (236 mg). 1H NMR δ 12.05 (bs, 1H) 9.57 (s, 1H) 6.21 (s, 1H) 3.67 (t, 4H) 3.57 (t, 4H) 2.22 (s, 3H); m/z 313.

Workup

  1. customThe precipitation
  2. filtrationwas filtered
  3. washwashed with cold ethanol
  4. customThe compound was dried by vacuum oven

Sources & evidence

ORD record
ord-36740e50314f498c804acdc95c271e73
Source dataset
uspto-grants-2012_01
Patent number
US08088784B2

Reaction notes

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