Dimethyl Sulfoxide → 5-{9-(Cyclopropylmethyl)-8-[4-(methylsulfonyl)piperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

HRID 421302Notes

Reaction equation

HRID 421302 reaction equation
CS(C)=O.Cl[C:6]1[N:7]([CH2:28][CH:29]2[CH2:31][CH2:30]2)[C:8]2[C:13]([N:14]=1)=[C:12]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)[N:11]=[C:10]([C:21]1[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=1)[N:9]=2.[S:32]([N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1)([CH3:35])(=[O:34])=[O:33]>ClCCl.CO>[CH:29]1([CH2:28][N:7]2[C:6]([N:39]3[CH2:40][CH2:41][N:36]([S:32]([CH3:35])(=[O:34])=[O:33])[CH2:37][CH2:38]3)=[N:14][C:13]3[C:8]2=[N:9][C:10]([C:21]2[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=2)=[N:11][C:12]=3[N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 7091611-(Methylsulfonyl)piperazine2×HCID 593335195-[8-chloro-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 453778635-{9-(Cyclopropylmethyl)-8-[4-(methylsulfonyl)piperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amineYield 68%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

A dimethyl sulfoxide solution (1.0 ml) of 5-[8-chloro-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amine (101.9 mg, 0.26 mmol) and N-mesylpiperazine (125.8 mg, 0.77 mmol) was heated at 140° C. and stirred for 4 hours followed by the addition of N-mesylpiperazine (83.8 mg, 0.51 mmol) and the resulting mixture was further stirred at 140° C. for 3 hours. The reaction mixture was left standing to cool followed by the addition of dichloromethane-methanol (10:1) and washed with saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate, the reaction mixture was filtrated, then the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=15:1) to give the title compound (89.2 mg, 68%) as a white solid.

Workup

  1. stirringthe resulting mixture was further stirred at 140° C. for 3 hours
  2. waitThe reaction mixture was left
  3. temperatureto cool
  4. washwashed with saturated aqueous sodium hydrogen carbonate solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationthe reaction mixture was filtrated
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=15:1)

Sources & evidence

ORD record
ord-82b2a9204489472a813e1ff34def164d
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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