Benzyl chloroformate → HCID 66602125, compound

HRID 336952Notes

Reaction equation

HRID 336952 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:11](=[O:28])[NH:10]2)=[C:5]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:4]=1)#[N:2].[H-].[Na+].Cl[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37]>C1COCC1>[C:15]([C:14]1[CH:9]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[S:29]([CH3:32])(=[O:31])=[O:30])[N:10]([C:36]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37])[C:11](=[O:28])[N:12]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)[C:13]=1[CH3:17])#[N:16]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 24758Sodium hydrideHCID 42642360(6s)-6-(4-Cyano-2-Methylsulfonyl-Phenyl)-4-Methyl-2-Oxidanylidene-3-[3-(Trifluoromethyl)phenyl]-1,6-Dihydropyrimidine-5-Carbonitrile

Product 1

HCID 66602125HCID 66602125, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The reaction was carried out under argon. (4S)-4-[4-Cyano-2-(methylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (115 mg, 250 μmol) was initially charged in dry THF (3 ml), and sodium hydride (60% in mineral oil; 14 mg, 350 μmol; 1.4 eq.) was added at 0° C. The mixture was warmed to RT and stirred for 20 min. A solution of benzyl chloroformate (60 mg, 350 μmol; 1.4 eq.) in THF (1 ml) was then slowly added dropwise. After a reaction time of 1.5 h, the reaction mixture was concentrated and the crude product was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave the title compound as a colorless solid (68 mg, 46% of theory).

Workup

  1. concentrationAfter a reaction time of 1.5 h, the reaction mixture was concentrated
  2. customthe crude product was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)

Sources & evidence

ORD record
ord-6b99884230cc4270bbe2ec679424e5b6
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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