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

HRID 1876592Notes

Reaction equation

HRID 1876592 reaction equation
C(N(CC)CC)C.C(Cl)Cl.[CH:11]1([CH2:14][N:15]2[C:23]([N:24]3[CH2:29][C@H:28]([CH3:30])[NH:27][C@H:26]([CH3:31])[CH2:25]3)=[N:22][C:21]3[C:16]2=[N:17][C:18]([C:38]2[CH:39]=[N:40][C:41]([NH2:44])=[N:42][CH:43]=2)=[N:19][C:20]=3[N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH2:13][CH2:12]1.[C:45](OC(=O)C)(=[O:47])[CH3:46]>C(Cl)Cl.CO.CN(C)C=O>[C:45]([N:27]1[C@@H:28]([CH3:30])[CH2:29][N:24]([C:23]2[N:15]([CH2:14][CH:11]3[CH2:13][CH2:12]3)[C:16]3[C:21]([N:22]=2)=[C:20]([N:32]2[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)[N:19]=[C:18]([C:38]2[CH:39]=[N:40][C:41]([NH2:44])=[N:42][CH:43]=2)[N:17]=3)[CH2:25][C@H:26]1[CH3:31])(=[O:47])[CH3:46]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 7918Acetic Anhydride2×HCID 8471TriethylamineHCID 453780135-[9-(cyclopropylmethyl)-8-(cis-3,5-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 593336335-{8-[4-Acetyl-cis-3,5-dimethylpiperazin-1-yl]-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amineYield 97%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Triethylamine (73.7 μl, 0.53 mmol) was added to a methylene chloride (10 ml)-dimethylformamide (1.5 ml) mixture solution of 5-{9-(cyclopropylmethyl)-8-[cis-3,5-dimethylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (102.3 mg, 0.22 mmol) at room temperature followed by the addition of acetic anhydride (24.9 μl, 0.26 mmol) with ice cooling. The resulting mixture was stirred at room temperature for 3 days followed by the addition of acetic anhydride (6.2 μl, 0.07 mmol) and the resulting mixture was further stirred for 3 days. The reaction mixture was poured into methylene chloride-methanol (10:1) and the resulting mixture was 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 0.10 give the title compound (107.7 mg, 97%) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was further stirred for 3 days
  2. washthe resulting mixture was washed 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) to 0.10

Sources & evidence

ORD record
ord-1fde658bfde04a8b9291288c051f6398
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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