Water → 9-benzyloxy-2-cyclopropylmethyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169478Notes

Reaction equation

HRID 2169478 reaction equation
[CH:1]1([CH2:4][N:5]([CH2:35][CH2:36]O)[C:6]([C:8]2[C:13]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:12]([OH:22])[N:11]=[C:10]([CH2:23][C:24]3([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[CH2:28][CH2:27][CH2:26][CH2:25]3)[N:9]=2)=[O:7])[CH2:3][CH2:2]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C(OCC)(=O)C.O>ClCCl>[CH2:15]([O:14][C:13]1[C:12](=[O:22])[N:11]=[C:10]([CH2:23][C:24]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[CH2:25][CH2:26][CH2:27][CH2:28]2)[N:9]2[CH2:36][CH2:35][N:5]([CH2:4][CH:1]3[CH2:3][CH2:2]3)[C:6](=[O:7])[C:8]=12)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178519975HCID 178519975, compound

Product 1

HCID 867261069-benzyloxy-2-cyclopropylmethyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 58.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylicacidcyclopropylmethyl-(2-hydroxyethyl)-amide (447) (80 mg, 0.159 mmol), in dichloromethane (5 mL), TPP (146.13 mg, 0.558 mmol) and diisopropyl azodicarboxylate (0.094 mL, 0.478 mmol) were added and stirring was continued for 1 h at room temperature while silica thin layer chromatography was performed (100% ethyl acetate; Rf=0.2). After completion of the reaction, water (5 mL) was added and the mixture was extracted with dichloromethane (2×30 mL) and the organic phase was dried and concentrated. The resulting crude product was purified by normal silica gel (100-200) column chromatography using 60-70% ethyl acetate in hexane as a gradient polarity mobile phase to get 9-benzyloxy-2-cyclopropylmethyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (448) (45.0 mg, 58%) as a white solid.

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with dichloromethane (2×30 mL)
  3. customthe organic phase was dried
  4. concentrationconcentrated
  5. customThe resulting crude product was purified by normal silica gel (100-200) column chromatography

Sources & evidence

ORD record
ord-7b7bcc13462b4c12bca3a82d43a214ca
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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