N-methyl-2-pyrrolidone → 5-[8-(3,3-Dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine

HRID 1876613Notes

Reaction equation

HRID 1876613 reaction equation
CN1CCCC1=O.Cl[C:9]1[N:10]([CH2:31][C:32]([F:35])([F:34])[F:33])[C:11]2[C:16]([N:17]=1)=[C:15]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[N:14]=[C:13]([C:24]1[CH:25]=[N:26][C:27]([NH2:30])=[N:28][CH:29]=1)[N:12]=2.[CH3:36][C:37]1([CH3:43])[CH2:42][NH:41][CH2:40][CH2:39][NH:38]1>C(Cl)Cl.CO>[CH3:36][C:37]1([CH3:43])[NH:38][CH2:39][CH2:40][N:41]([C:9]2[N:10]([CH2:31][C:32]([F:34])([F:33])[F:35])[C:11]3[C:16]([N:17]=2)=[C:15]([N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)[N:14]=[C:13]([C:24]2[CH:25]=[N:26][C:27]([NH2:30])=[N:28][CH:29]=2)[N:12]=3)[CH2:42]1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 146641862,2-DimethylpiperazineHCID 593335342-(2-aminopyrimidin-5-yl)-8-chloro-6-(morpholin-4-yl)-9-(2,2,2-trifluoroethyl)-9H-purine

Product 1

HCID 593335975-[8-(3,3-Dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amineYield 95%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
120 °C

Procedure

An N-methyl-2-pyrrolidone suspension (5.0 ml) of 5-[8-chloro-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (492.8 mg, 1.19 mmol) and 2,2-dimethylpiperazine (JMC, 1995, Vol. 38, No. 22, 4389) (571.3 mg, 4.75 mmol) was heated at 120° C. to dissolve and the resulting mixture was stirred at 100° C. for 12 hours. The resulting mixture was left standing to cool, poured into methylene chloride-methanol (10:1), and 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 medium pressure silica gel column chromatography (methylene chloride:methanol=49:1 to 13:1) to give the title compound (554.4 mg, 95%) as a pale yellow solid.

Workup

  1. dissolutionto dissolve
  2. waitThe resulting 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 mixture was filtrated
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by medium pressure silica gel column chromatography (methylene chloride:methanol=49:1 to 13:1)

Sources & evidence

ORD record
ord-c5fc3be782bc43a0bd2401c3535c4189
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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