Tetrahydrofuran → 4-[2-(2-Aminopyrimidin-5-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-8-yl]-cis-2,6-dimethylpiperazine-1-carboaldehyde

HRID 1876606Notes

Reaction equation

HRID 1876606 reaction equation
[CH3:1][C@H:2]1[NH:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[N:10]([CH2:31][C:32]([F:35])([F:34])[F:33])[C:11]3[C:16]([N:17]=2)=[C:15]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:14]=[C:13]([C:24]2[CH:25]=[N:26][C:27]([NH2:30])=[N:28][CH:29]=2)[N:12]=3)[CH2:3]1.[O:36]1CCC[CH2:37]1.CN(CCS(O)(=O)=O)C>C(Cl)Cl>[NH2:30][C:27]1[N:28]=[CH:29][C:24]([C:13]2[N:12]=[C:11]3[C:16]([N:17]=[C:9]([N:4]4[CH2:3][C@@H:2]([CH3:1])[N:7]([CH:37]=[O:36])[C@@H:6]([CH3:8])[CH2:5]4)[N:10]3[CH2:31][C:32]([F:35])([F:34])[F:33])=[C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:14]=2)=[CH:25][N:26]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2370422-(Dimethylamino)ethanesulfonic acid2×HCID 453780145-[8-(cis-3,5-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 593335684-[2-(2-Aminopyrimidin-5-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-8-yl]-cis-2,6-dimethylpiperazine-1-carboaldehydeYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-[8-(cis-3,5-Dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (101.7 mg, 0.21 mmol) were added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (33.8 mg, 0.21 mmol) at room temperature and the resulting mixture was stirred for 1 day. 1H-Benzotriazole-1-carboxyaldehyde (5.1 mg, 0.03 mmol) was added, the resulting mixture was further stirred for 1 day, and then the reaction mixture was poured into methylene chloride and washed with a 2 N aqueous sodium hydroxide 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 preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (98.0 mg, 91%) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was further stirred for 1 day
  2. washwashed with a 2 N aqueous sodium hydroxide solution
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationthe mixture was filtrated
  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-e3d64138d0924169b374e03691d343e0
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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