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

HRID 2169390Notes

Reaction equation

HRID 2169390 reaction equation
[CH:1]1([N:4]([CH2:38][CH2:39]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[C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[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.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl.C(OCC)(=O)C>[CH2:14]([O:13][C:12]1[C:11](=[O:21])[N:10]=[C:9]([CH2:22][C:23]2([C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:8]2[CH2:39][CH2:38][N:4]([CH:1]3[CH2:3][CH2:2]3)[C:5](=[O:6])[C:7]=12)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178519957N-cyclopropyl-N-(2-hydroxyethyl)-2-[(1-naphthalen-1-ylcyclopentyl)methyl]-4-oxo-5-phenylmethoxy-1H-pyrimidine-6-carboxamide

Product 1

HCID 867260219-benzyloxy-2-cyclopropyl-6-(1-naphthalen-1-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 92.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid cyclopropyl-(2-hydroxyethyl)-amide (355) (120 mg, 0.22 mmol) and diisopropyl azodicarboxylate (0.22 mL, 1.12 mmol) in dichloromethane (30 mL) was added triphenyl phosphine (351 mg, 1.34 mmol) at room temperature and the reaction mixture was stirred for 15 min at the same temperature. The yellow color disappeared (silica TLC 5% methanol in ethyl acetate, Rf=0.2). The dichloromethane was removed in vacuo and the crude mass was purified by silica gel (normal, 100-200 mesh) column chromatography using a gradient eluent mixture of 1% to 5% methanol in dichloromethane to get pure 9-benzyloxy-2-cyclopropyl-6-(1-naphthalen-1-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (356) (106 mg, 92%) as a white solid.

Workup

  1. customThe dichloromethane was removed in vacuo
  2. customthe crude mass was purified by silica gel (normal, 100-200 mesh) column chromatography
  3. additiona gradient eluent mixture of 1% to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-6fe51444eb834021a14c70493beacaaf
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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