Dimethyl Sulfoxide → 5-[9-(Cyclopropylmethyl)-6,8-dimorpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amine

HRID 1876516Notes

Reaction equation

HRID 1876516 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.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>ClCCl.CO>[CH:29]1([CH2:28][N:7]2[C:6]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]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 8083Morpholine2×HCID 593335195-[8-chloro-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 593335745-[9-(Cyclopropylmethyl)-6,8-dimorpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amineYield 103.3%

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 (75.3 mg, 0.19 mmol) and morpholine (65.8 μl, 0.75 mmol) was heated at 140° C. and stirred for 4 hours. Morpholine (32.9 μl, 0.38 mmol) was added at room temperature and the resulting mixture was further stirred at 140° C. for 2 hours. The resulting mixture was left standing to cool followed by the addition of dichloromethane-methanol (10:1) and the resulting mixture was washed with saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, 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 (85.9 mg, 100%) as a white solid.

Workup

  1. stirringthe resulting mixture was further stirred at 140° C. for 2 hours
  2. waitThe resulting mixture was left
  3. temperatureto cool
  4. washthe resulting mixture was washed with saturated aqueous sodium hydrogen carbonate solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationthe 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-d9f1f2d362864ae38f72c568f2e54707
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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