1,4,5,6-Tetrahydropyrimidin-2-amine → (2S)-2-benzyloxycarbonylamino-3-{9-[3-(1,4,5,6-tetrahydro-pyrimidin-2-ylcarbamoyl)-propyl]-9H-purin-6-ylamino}-propionic acid tert-butyl ester

HRID 854248Notes

Reaction equation

HRID 854248 reaction equation
C([O:3][C:4](=O)[CH2:5][CH2:6][CH2:7][N:8]1[CH:16]=[N:15][C:14]2[C:9]1=[N:10][CH:11]=[N:12][C:13]=2[NH:17][CH2:18][C@H:19]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])C.[NH:39]1[CH2:44][CH2:43][CH2:42][N:41]=[C:40]1[NH2:45]>CN(C)C=O>[C:23]([O:22][C:20](=[O:21])[C@@H:19]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[CH2:18][NH:17][C:13]1[N:12]=[CH:11][N:10]=[C:9]2[C:14]=1[N:15]=[CH:16][N:8]2[CH2:7][CH2:6][CH2:5][C:4](=[O:3])[NH:45][C:40]1[NH:41][CH2:42][CH2:43][CH2:44][N:39]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

4

Reactant 2

HCID 32874121,4,5,6-Tetrahydropyrimidin-2-amineHCID 155472654-[6-((2S)-2-Benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethylamino)-purin-9-yl]-butyric acid ethyl ester

Product 1

HCID 15547266(2S)-2-benzyloxycarbonylamino-3-{9-[3-(1,4,5,6-tetrahydro-pyrimidin-2-ylcarbamoyl)-propyl]-9H-purin-6-ylamino}-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

200 mg (0.38 mmol) of 4-[6-((2S)-2-benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethylamino)-purin-9-yl]-butyric acid ethyl ester was dissolved in 2 ml of dimethylformamide and 188 mg (1.9 mmol) of 1,4,5,6-tetrahydro-pyrimidin-2-ylamine was added. The solution was stirred at room temperature for 16 hours. The solvent was removed in vacuo, the residue was dissolved in dichloromethane and the solution was washed twice with 10% aqueous citric acid solution and twice with water. Product in the combined aqueous phase was extracted five times with dichloromethane. The combined organic phase was dried with sodium sulfate, filtered and the solvent was removed in vacuo. The residue was chromatographed on silica gel eluting with dichloromethane/methanol (10/1), followed by DCM/AcOH/water (85:15:1.5:1.5). Yield: 70.6 mg.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washthe solution was washed twice with 10% aqueous citric acid solution and twice with water
  4. extractionProduct in the combined aqueous phase was extracted five times with dichloromethane
  5. dry with materialThe combined organic phase was dried with sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo
  8. customThe residue was chromatographed on silica gel eluting with dichloromethane/methanol (10/1)

Sources & evidence

ORD record
ord-e8d6a6406aee412594ac30ea19a7d3fd
Source dataset
uspto-grants-2007_08
Patent number
US07259159B2

Reaction notes

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