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

HRID 1876576Notes

Reaction equation

HRID 1876576 reaction equation
[CH:1]([N:4](C(C)C)CC)(C)C.[CH3:10][N:11]1[CH2:15][CH2:14][CH2:13][C:12]1=O.[NH2:17][C:18]1[N:23]=[CH:22][C:21]([C:24]2[N:32]=[C:31]3[C:27]([N:28]=[C:29](Cl)[N:30]3[CH2:33][C:34]([F:37])([F:36])[F:35])=[C:26]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[N:25]=2)=[CH:20][N:19]=1>O>[CH2:14]([C@H:13]1[NH:4][CH2:1][CH2:10][N:11]([C:29]2[N:30]([CH2:33][C:34]([F:35])([F:37])[F:36])[C:31]3[C:27]([N:28]=2)=[C:26]([N:39]2[CH2:40][CH2:41][O:42][CH2:43][CH2:44]2)[N:25]=[C:24]([C:21]2[CH:22]=[N:23][C:18]([NH2:17])=[N:19][CH:20]=2)[N:32]=3)[CH2:12]1)[CH3:15]

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 593335385-{8-[(3R)-3-Ethylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Diisopropylethylamine (1.91 ml, 10.98 mmol) was added to an N-methyl-2-pyrrolidone suspension (5 ml) of 2-(R)-ethylpiperazine-2-hydrochloride (751 mg) and 2-(2-aminopyrimidin-5-yl)-8-chloro-6-(morpholin-4-yl)-9-(2,2,2-trifluoroethyl)-9H-purine (506 mg, 1.22 mmol) and the resulting mixture was heated at 100° C. and stirred for 5 days. Water was added to the reaction mixture and the resulting mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with water and saturated brine, and dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (chloroform:methanol=97:3 to 90:10) to give the title compound (562 mg) as a pale yellow solid.

Workup

  1. extractionthe resulting mixture was extracted twice with ethyl acetate
  2. washwashed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationthe mixture was filtrated
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica gel chromatography (chloroform:methanol=97:3 to 90:10)

Sources & evidence

ORD record
ord-692108c00e06444584634f23421eaca2
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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