Triphenylphosphine → 9-benzyloxy-2-cyclopropyl-6-(1-phenyl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169318Notes

Reaction equation

HRID 2169318 reaction equation
[CH:1]1([N:4]([CH2:34][CH2:35]O)[C:5]([C:7]2[C:12]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11]([OH:21])[N:10]=[C:9]([CH2:22][C:23]3([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:27][CH2:26][CH2:25][CH2:24]3)[N:8]=2)=[O:6])[CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[CH2:14]([O:13][C:12]1[C:11](=[O:21])[N:10]=[C:9]([CH2:22][C:23]2([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:8]2[CH2:35][CH2:34][N:4]([CH:1]3[CH2:2][CH2:3]3)[C:5](=[O:6])[C:7]=12)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178519962HCID 178519962, compound

Product 1

HCID 867259579-benzyloxy-2-cyclopropyl-6-(1-phenyl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 62.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid cyclopropyl-(2-hydroxyethyl)-amide (285) (300 mg, 0.62 mmol) in dichloromethane (30 mL) were added triphenyl phosphine (242 mg, 0.92 mmol) and diisopropyl azodicarboxylate (0.2 mL, 1.23 mmol) at room temperature. Stirring was continued for 10 min at room temperature. The reaction mixture was concentrated under reduced pressure to get a crude product, which was purified by Combi-Flash column (triphenyl phosphine oxide was eluted in ethyl acetate and the product was eluted at 2% methanol in dichloromethane). It was again purified by preparative TLC plate to remove traces of triphenyl phosphine oxide (mobile phase: ethyl acetate) and 9-benzyloxy-2-cyclopropyl-6-(1-phenyl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (286) (180 mg, 62.3%) was obtained as a white sticky solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto get a crude product, which
  3. customwas purified by Combi-Flash column (triphenyl phosphine oxide
  4. washwas eluted in ethyl acetate
  5. washthe product was eluted at 2% methanol in dichloromethane)
  6. customIt was again purified by preparative TLC plate
  7. customto remove traces of triphenyl phosphine oxide (mobile phase: ethyl acetate)

Sources & evidence

ORD record
ord-2404fa5399b3419892948e761e014c6d
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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