p-Toluenesulfonic acid → 2-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide

HRID 929909Notes

Reaction equation

HRID 929909 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=2)[N:3]=1.[NH2:21][CH2:22][C:23]1[C:30]([F:31])=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=1[F:32].CC1C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[C:27]([C:26]1[CH:25]=[C:24]([F:32])[C:23]([CH2:22][NH:21][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]3[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=3)[N:3]=2)=[C:30]([F:31])[CH:29]=1)#[N:28]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 219055604-(Aminomethyl)-3,5-difluorobenzonitrileHCID 900240272-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide

Product 1

HCID 727064692-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide (120 mg, 0.41 mmol) (II-1, prepared by Procedure D), 4-(aminomethyl)-3,5-difluorobenzonitrile (68 mg, 0.41 mmol) (III-1, prepared by Procedure E) and TsOH (56 mg, 0.33 mmol) in dioxane (2 mL) was heated to 160° C. for 2 h then concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with Na2CO3(aq), dried (Na2SO4), concentrated in vacuo and purified by prep. TLC (5-10% v/v MeOH/DCM) to afford 2-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide I-1 (50 mg, 29%) as a white solid. LC-MS (Method A), RT=8.02 min. (ES+) 427.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with Na2CO3(aq)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by prep

Sources & evidence

ORD record
ord-a6ef61f3edfd4753a41c7eadd4cdf7cc
Source dataset
uspto-grants-2016_03
Patent number
US09296725B2

Reaction notes

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