Dichloromethane → 5-[8-(4-Acetyl-3,3-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine

HRID 421428Notes

Reaction equation

HRID 421428 reaction equation
C(N(CC)CC)C.[C:8](OC(=O)C)(=[O:10])[CH3:9].C(Cl)Cl.[CH3:18][C:19]1([CH3:52])[NH:24][CH2:23][CH2:22][N:21]([C:25]2[N:26]([CH2:47][C:48]([F:51])([F:50])[F:49])[C:27]3[C:32]([N:33]=2)=[C:31]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)[N:30]=[C:29]([C:40]2[CH:41]=[N:42][C:43]([NH2:46])=[N:44][CH:45]=2)[N:28]=3)[CH2:20]1>C(Cl)Cl.CO>[C:8]([N:24]1[CH2:23][CH2:22][N:21]([C:25]2[N:26]([CH2:47][C:48]([F:51])([F:49])[F:50])[C:27]3[C:32]([N:33]=2)=[C:31]([N:34]2[CH2:35][CH2:36][O:37][CH2:38][CH2:39]2)[N:30]=[C:29]([C:40]2[CH:45]=[N:44][C:43]([NH2:46])=[N:42][CH:41]=2)[N:28]=3)[CH2:20][C:19]1([CH3:52])[CH3:18])(=[O:10])[CH3:9]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 7918Acetic Anhydride2×HCID 8471TriethylamineHCID 593335975-[8-(3,3-Dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 593336685-[8-(4-Acetyl-3,3-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amineYield 88%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Triethylamine (72.8 μl, 0.52 mmol) and acetic anhydride (24.6 μl, 0.26 mmol) were added to a methylene chloride solution (3.0 ml) of 5-[8-(3,3-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (107.2 mg, 0.22 mmol) with ice cooling. The resulting mixture was stirred at room temperature for 2 hours followed by the addition of acetic anhydride (4.1 μl, 0.04 mmol) with ice cooling and the resulting mixture was stirred at room temperature for 4.5 hours. The reaction mixture was poured into methylene chloride-methanol (10:1), washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (102.6 mg, 88%) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 4.5 hours
  2. washwashed with saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

Sources & evidence

ORD record
ord-4cca5f73aa124fc0b20b74b20dcde147
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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