Triphenylphosphine → 9-(benzyloxy)-6-((1-(4-chlorophenyl)cyclopentyl)methyl)-2-(1,1,1-trifluoropropan-2-yl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dione

HRID 2169186Notes

Reaction equation

HRID 2169186 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:29]([N:31]([CH2:38][CH2:39]O)[CH:32]([CH3:37])[C:33]([F:36])([F:35])[F:34])=[O:30])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]2[CH2:39][CH2:38][N:31]([CH:32]([CH3:37])[C:33]([F:35])([F:34])[F:36])[C:29](=[O:30])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178464479HCID 178464479, compound

Product 1

HCID 867258379-(benzyloxy)-6-((1-(4-chlorophenyl)cyclopentyl)methyl)-2-(1,1,1-trifluoropropan-2-yl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dioneYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-(benzyloxy)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxy-N-(2-hydroxyethyl)-N-(1,1,1-trifluoropropan-2-yl)pyrimidine-4-carboxamide (43) (102 mg, 176 μmol, Eq: 1.00) in dichloromethane (5 ml) was added triphenylphosphine (69.4 mg, 265 μmol, Eq: 1.5) at room temperature and the reaction mixture was stirred for 10 min. Then diisopropyl azodicarboxylate (53.5 mg, 51.5 μl, 265 μmol, Eq: 1.5) was added and the reaction mixture was stirred for 18 hrs at room temperature, concentrated, and chromatographed (silica gel, gradient, 0 to 5% methanol-dichloromethane) to obtain 9-(benzyloxy)-6-((1-(4-chlorophenyl)cyclopentyl)methyl)-2-(1,1,1-trifluoropropan-2-yl)-3,4-dihydro-1H-pyrazino[1,2-c]pyrimidine-1,8(2H)-dione (44) (white foam, 90.8 mg, 162 μmol, 91.9% yield).

Workup

  1. stirringthe reaction mixture was stirred for 18 hrs at room temperature
  2. concentrationconcentrated
  3. customchromatographed (silica gel, gradient, 0 to 5% methanol-dichloromethane)

Sources & evidence

ORD record
ord-34cb5df59a2f4d839856e34728db55e7
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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