Water → 1-(4-Amino-5-fluoro-pyrimidin-2-yl)-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (adamantan-1-ylmethyl)-amide

HRID 2279608Notes

Reaction equation

HRID 2279608 reaction equation
[C:1]12([CH2:11][NH:12][C:13]([C:15]3[C:16]([C:20]([F:23])([F:22])[F:21])=[N:17][NH:18][CH:19]=3)=[O:14])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.Cl[C:25]1[N:30]=[C:29]([NH2:31])[C:28]([F:32])=[CH:27][N:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN1C(=O)CCC1>[C:1]12([CH2:11][NH:12][C:13]([C:15]3[C:16]([C:20]([F:23])([F:22])[F:21])=[N:17][N:18]([C:25]4[N:30]=[C:29]([NH2:31])[C:28]([F:32])=[CH:27][N:26]=4)[CH:19]=3)=[O:14])[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 2543722-Chloro-5-fluoropyrimidin-4-amineHCID 178522750HCID 178522750, compound

Product 1

HCID 595800161-(4-Amino-5-fluoro-pyrimidin-2-yl)-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (adamantan-1-ylmethyl)-amide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (adamantan-1-ylmethyl)-amide (100 mg, 0.306 mmol), 2-chloro-5-fluoro-pyrimidin-4-ylamine (52 mg, 0.35 mmol) and Cs2CO3 (130 mg, 0.4 mmol) in NMP (1.0 mL) is heated in a microwave reactor at 150° C. for 1 h. The mixture is poured into H2O. The crude product is filtered out, dissolved in 10% MeOH in DCM, and dried over anhydrous Na2SO4. The title compound is purified by PTLC (eluted with 5% MeOH in DCM). 1H NMR (CD3OD): 8.96 (s, 1H), 8.11 (s, 1H), 3.0 (s, 2H), 1.98 (m, 3H), 1.78-1.68 (m, 6H), 1.58 (s, 611). MS (M+1)=439.29; RT=1.34 min. *IC50.

Workup

  1. filtrationThe crude product is filtered out
  2. dissolutiondissolved in 10% MeOH in DCM
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe title compound is purified by PTLC (eluted with 5% MeOH in DCM)

Sources & evidence

ORD record
ord-8faa5e81769d48a18cab445c2bfb0856
Source dataset
uspto-grants-2015_09
Patent number
US09133204B2

Reaction notes

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