p-Toluenesulfonic acid → 3-cyclopropyl-3-[4-(5-methoxy-2-{[3-(1,3-oxazol-5-yl)phenyl]amino}pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

HRID 1876897Notes

Reaction equation

HRID 1876897 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH:13]([CH:17]3[CH2:19][CH2:18]3)[CH2:14][C:15]#[N:16])[CH:12]=2)[C:5]([O:20][CH3:21])=[CH:4][N:3]=1.[O:22]1[C:26]([C:27]2[CH:28]=[C:29]([CH:31]=[CH:32][CH:33]=2)[NH2:30])=[CH:25][N:24]=[CH:23]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O1CCOCC1>C(#N)C.O>[CH:17]1([CH:13]([N:11]2[CH:12]=[C:8]([C:6]3[C:5]([O:20][CH3:21])=[CH:4][N:3]=[C:2]([NH:30][C:29]4[CH:31]=[CH:32][CH:33]=[C:27]([C:26]5[O:22][CH:23]=[N:24][CH:25]=5)[CH:28]=4)[N:7]=3)[CH:9]=[N:10]2)[CH2:14][C:15]#[N:16])[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 312751,4-DioxaneHCID 27392893-(1,3-Oxazol-5-yl)anilineHCID 866373033-[4-(2-chloro-5-methoxypyrimidin-4-yl)-1H-pyrazol-1-yl]-3-cyclopropylpropanenitrile

Product 1

HCID 580146553-cyclopropyl-3-[4-(5-methoxy-2-{[3-(1,3-oxazol-5-yl)phenyl]amino}pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-[4-(2-chloro-5-methoxypyrimidin-4-yl)-1H-pyrazol-1-yl]-3-cyclopropylpropanenitrile (20 mg, 0.00008 mol), 3-(1,3-oxazol-5-yl)aniline (18.1 mg, 0.000113 mol), and p-toluenesulfonic acid (11 mg, 0.000064 mol) in dry 1,4-dioxane (0.5 mL, 0.006 mol) was refluxed overnight. The mixture was diluted with acetonitrile and water, purified on RP-HPLC at pH 10 to give the desired product as a racemic mixture (free base). LCMS (M+H) 428.1.

Workup

  1. temperaturewas refluxed overnight
  2. custompurified on RP-HPLC at pH 10

Sources & evidence

ORD record
ord-d686a13dad3b47e5a07e4e5f506cf4c4
Source dataset
uspto-grants-2012_11
Patent number
US08309718B2

Reaction notes

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