4-Biphenylyl isocyanate → biphenyl-4-yl-carbamic acid 3-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-cyclopentyl ester

HRID 417829Notes

Reaction equation

HRID 417829 reaction equation
[F:1][C:2]1[C:3]([N:15]=CN(C)C)=[N:4][C:5](=[O:14])[N:6]([CH:8]2[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]2)[CH:7]=1.[CH:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([N:32]=[C:33]=[O:34])=[CH:28][CH:27]=2)=[CH:22][CH:21]=1>C(Cl)Cl.CN(C)C=O>[NH2:15][C:3]1[C:2]([F:1])=[CH:7][N:6]([CH:8]2[CH2:12][CH2:11][CH:10]([O:13][C:33](=[O:34])[NH:32][C:29]3[CH:28]=[CH:27][C:26]([C:23]4[CH:24]=[CH:25][CH:20]=[CH:21][CH:22]=4)=[CH:31][CH:30]=3)[CH2:9]2)[C:5](=[O:14])[N:4]=1

Participants

5

Reactant 2

HCID 36123194-Biphenylyl isocyanateHCID 66649234N'-[5-Fluoro-1-(3-hydroxy-cyclopentyl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-N,N-dimethyl-formamidine

Product 1

HCID 66649316biphenyl-4-yl-carbamic acid 3-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-cyclopentyl esterYield 38.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of N′-[5-fluoro-1-(3-hydroxy-cyclopentyl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-N,N-dimethyl-formamidine (0.050 g, 0.186 mmol) in CH2Cl2 (2 mL) and anhydrous dimethylformamide (1 mL) was treated with 4-biphenyl isocyanate (0.039 g, 0.2 mmol). The mixture was stirred at room temperature under nitrogen for 5 hours, then quenched by the addition of acetic acid (0.5 mL) and stirred 10 minutes. The mixture was concentrated in vacuo, loaded on silica gel, and chromatographed on silica gel (10 g SiO2, 8:1 ethyl acetate/methanol) to afford biphenyl-4-yl-carbamic acid 3-(4-amino-5-fluoro-2-oxo-2H-pyrimidin-1-yl)-cyclopentyl ester 31 as a white solid (0.029 g, 38%).

Workup

  1. customquenched by the addition of acetic acid (0.5 mL)
  2. stirringstirred 10 minutes
  3. concentrationThe mixture was concentrated in vacuo
  4. customchromatographed on silica gel (10 g SiO2, 8:1 ethyl acetate/methanol)

Sources & evidence

ORD record
ord-8bcbdee4769542a6b08e1fd9ed58b0ea
Source dataset
uspto-grants-2012_01
Patent number
US08093245B2

Reaction notes

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