Tetrahydrofuran → (2R)-4-[2-(2-Aminopyrimidin-5-yl)-9-isobutyl-6-morpholin-4-yl-9H-purin-8-yl]-2-methylpiperazine-1-carboaldehyde

HRID 1876594Notes

Reaction equation

HRID 1876594 reaction equation
[CH2:1]([N:5]1[C:13]([N:14]2[CH2:19][CH2:18][NH:17][C@H:16]([CH3:20])[CH2:15]2)=[N:12][C:11]2[C:6]1=[N:7][C:8]([C:27]1[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=1)=[N:9][C:10]=2[N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)[CH:2]([CH3:4])[CH3:3].[O:34]1CCC[CH2:35]1.CN(CCS(O)(=O)=O)C.[OH-].[Na+]>C(Cl)Cl>[NH2:33][C:30]1[N:31]=[CH:32][C:27]([C:8]2[N:7]=[C:6]3[C:11]([N:12]=[C:13]([N:14]4[CH2:19][CH2:18][N:17]([CH:35]=[O:34])[C@H:16]([CH3:20])[CH2:15]4)[N:5]3[CH2:1][CH:2]([CH3:4])[CH3:3])=[C:10]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:9]=2)=[CH:28][N:29]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 2370422-(Dimethylamino)ethanesulfonic acidHCID 593335435-{9-Isobutyl-8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

Product 1

HCID 45376103(2R)-4-[2-(2-Aminopyrimidin-5-yl)-9-isobutyl-6-morpholin-4-yl-9H-purin-8-yl]-2-methylpiperazine-1-carboaldehydeYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-{9-Isobutyl-8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (109.5 mg, 0.24 mmol) was added to a tetrahydrofuran solution (7.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (39.6 mg, 0.24 mmol) at room temperature and the resulting mixture was stirred for 70 minutes. Methylene chloride was added to the reaction mixture and the resulting mixture was poured into a 2 N aqueous sodium hydroxide solution and extracted with methylene chloride. 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 (107.9 mg, 93%) as a pale yellow solid.

Workup

  1. extractionextracted with methylene chloride
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationthe mixture was filtrated
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

Sources & evidence

ORD record
ord-44262a2a85264743b66f5815e9b1b3e8
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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