N-methyl-2-pyrrolidone → HCID 59333566, compound

HRID 421424Notes

Reaction equation

HRID 421424 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C:3]1=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.[CH:36]([N:39](C(C)C)CC)(C)C>C(Cl)Cl.CO>[CH2:4]1[C:5]2([CH2:6][N:2]([C:9]3[N:10]([CH2:31][C:32]([F:35])([F:34])[F:33])[C:11]4[C:16]([N:17]=3)=[C:15]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[N:14]=[C:13]([C:24]3[CH:29]=[N:28][C:27]([NH2:30])=[N:26][CH:25]=3)[N:12]=4)[CH2:1][CH2:36][NH:39]2)[CH2:3]1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 593335342-(2-aminopyrimidin-5-yl)-8-chloro-6-(morpholin-4-yl)-9-(2,2,2-trifluoroethyl)-9H-purine

Product 1

HCID 59333566HCID 59333566, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
100 °C

Procedure

Potassium carbonate (1.19 g, 8.58 mmol) was added to a methanol solution (10 ml) of 4-(trifluoroacetyl)-4,7-diazaspiro[2.5]octane hydrochloride (1.0 g, 4.09 mmol) at room temperature and the resulting mixture was stirred at 50° C. for 16 hours. The resulting mixture was left standing to cool, then potassium carbonate was removed by filtration, and the filtrate was concentrated to give crude 4,7-diazaspiro[2.5]octane. This compound was added to an N-methyl-2-pyrrolidone suspension of 5-[8-chloro-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (277.4 mg, 0.67 mmol) and dissolved at 120° C. followed by the addition of diisopropylethylamine (1.16 ml, 6.69 mmol) and the resulting mixture was stirred at 100° C. for 4 days. The resulting mixture was left standing to cool, then 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=24:1 to 12:1) to give the title compound (83.3 mg, 26%) as a brown amorphous solid.

Workup

  1. dissolutiondissolved at 120° C.
  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=24:1 to 12:1)

Sources & evidence

ORD record
ord-78d878cfee9f4944832e662fa0db4255
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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