2-Bromo-N-methylacetamide → (S)-2-(3-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)piperidin-1-yl)-N-methylacetamide

HRID 536390Notes

Reaction equation

HRID 536390 reaction equation
[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]3)=[CH:11][C:10]=2[CH3:22])=[N:6][CH:7]=1.Br[CH2:31][C:32]([NH:34][CH3:35])=[O:33]>CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[C:10]([CH3:22])=[CH:11][C:12]([C@@H:16]3[CH2:21][CH2:20][CH2:19][N:18]([CH2:31][C:32]([NH:34][CH3:35])=[O:33])[CH2:17]3)=[C:13]([CH3:15])[CH:14]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 154907452-Bromo-N-methylacetamideHCID 446112155-chloro-N2-(2,5-dimethyl-4-(piperidin-3-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 58255105(S)-2-(3-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)piperidin-1-yl)-N-methylacetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-chloro-N2-(2,5-dimethyl-4-(piperidin-3-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (700 mg, 1.70 mmol), 2-bromo-N-methylacetamide (258 mg, 1.70 mmol) and TEA (1.2 mL, 8.5 mmol) in DMF (4 mL) was stirred at rt for 30 min. The reaction was purified by RP-HPLC to give the product as a racemate; ESMS m/z 483.2 (M+1). Chiral separation of the racemic mixture was conducted with chiral HPLC (ChiralCel OD-H, Hex:EtOH:MeOH/80:10:10, 15 min run time, 1 mL/min). The two purified enantiomer peaks were collected separately, both as white solids: (R)-2-(3-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)piperidin-1-yl)-N-methylacetamide and (S)-2-(3-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)piperidin-1-yl)-N-methylacetamide; both peaks: ESMS m/z 483.2 (M+H+). The earlier eluting peak (rt=5.63 min. vs. rt=7.62 min.) was arbitrarily assigned as the (R) enantiomer.

Workup

  1. customThe reaction was purified by RP-HPLC
  2. customto give the product as a racemate
  3. customChiral separation of the racemic mixture
  4. customwas conducted with chiral HPLC (ChiralCel OD-H, Hex:EtOH:MeOH/80:10:10, 15 min run time, 1 mL/min)
  5. customThe two purified enantiomer peaks were collected separately
  6. washThe earlier eluting peak (rt=5.63 min. vs. rt=7.62 min.)

Sources & evidence

ORD record
ord-402ae106531a4965b7ee3d4e5055d5f0
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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