Triethylamine → 5-{9-(Cyclopropylmethyl)-8-[cis-3,5-dimethyl-4-(methylsulfonyl)piperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

HRID 421347Notes

Reaction equation

HRID 421347 reaction equation
C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[CH:13]1([CH2:16][N:17]2[C:25]([N:26]3[CH2:31][C@H:30]([CH3:32])[NH:29][C@H:28]([CH3:33])[CH2:27]3)=[N:24][C:23]3[C:18]2=[N:19][C:20]([C:40]2[CH:41]=[N:42][C:43]([NH2:46])=[N:44][CH:45]=2)=[N:21][C:22]=3[N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)[CH2:15][CH2:14]1>ClCCl.ClCCl.CO>[CH:13]1([CH2:16][N:17]2[C:25]([N:26]3[CH2:31][C@H:30]([CH3:32])[N:29]([S:9]([CH3:8])(=[O:11])=[O:10])[C@H:28]([CH3:33])[CH2:27]3)=[N:24][C:23]3[C:18]2=[N:19][C:20]([C:40]2[CH:41]=[N:42][C:43]([NH2:46])=[N:44][CH:45]=2)=[N:21][C:22]=3[N:34]2[CH2:35][CH2:36][O:37][CH2:38][CH2:39]2)[CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 8471Triethylamine3×HCID 31297Methanesulfonyl chloride3×HCID 453780135-[9-(cyclopropylmethyl)-8-(cis-3,5-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 593336365-{9-(Cyclopropylmethyl)-8-[cis-3,5-dimethyl-4-(methylsulfonyl)piperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amineYield 13.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

Triethylamine (127.1 μl, 0.91 mmol) and methanesulfonyl chloride (35.3 ml, 0.46 mmol) were added to a dichloromethane suspension (2.0 ml) of 5-[9-(cyclopropylmethyl)-8-(cis-3,5-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amine (105.9 mg, 0.23 mmol) with ice cooling and the resulting mixture was stirred at the same temperature for 2.5 hours and at room temperature for 4 hours. Triethylamine (127.1 μl, 0.91 mmol) and methanesulfonyl chloride (35.3 ml, 0.46 mmol) were added at room temperature and the resulting mixture was stirred for 16 hours followed by the addition of dichloromethane-methanol (10:1) and washed with water. 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 dissolved in 1,2-dichloroethane (2.0 ml). Triethylamine (127.1 μl, 0.91 mmol) and methanesulfonyl chloride (35.3 ml, 0.46 mmol) were added at room temperature and the resulting mixture was stirred for 19 hours followed by the addition of dichloromethane and washed with 10% aqueous citric acid 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=10:1) to give the title compound (16.3 mg, 13%) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was stirred for 16 hours
  2. washwashed with water
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationthe mixture was filtrated
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionthe resulting residue was dissolved in 1,2-dichloroethane (2.0 ml)
  7. stirringthe resulting mixture was stirred for 19 hours
  8. washwashed with 10% aqueous citric acid solution
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. filtrationthe mixture was filtrated
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customthe resulting residue was purified by preparative thin layer silica gel chromatography (dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-dbd28960a1c443408b4440196716e7af
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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