Pyridine → HCID 86650725, compound

HRID 2064386Notes

Reaction equation

HRID 2064386 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].[F:33][C:34]([F:45])([F:44])[C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1.N1C=CC=CC=1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[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])[N:10]2[C:39]2[CH:38]=[CH:37][CH:36]=[C:35]([C:34]([F:45])([F:44])[F:33])[CH:40]=2)=[C:5]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 42642360(6s)-6-(4-Cyano-2-Methylsulfonyl-Phenyl)-4-Methyl-2-Oxidanylidene-3-[3-(Trifluoromethyl)phenyl]-1,6-Dihydropyrimidine-5-Carbonitrile

Product 1

HCID 86650725HCID 86650725, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

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 (100 mg, 217 μmol), 3-(trifluoromethyl)phenylboronic acid (165 mg, 869 μmol; 4 eq.), copper(II) acetate (158 mg, 869 μmol; 4 eq.) and 4 Å molecular sieve (500 mg) were initially charged in dichloromethane (5 ml), pyridine (281 μl; 16 eq.) and triethylamine (121 μl; 4 eq.) were added and the mixture was subsequently stirred at RT for 20 h. The reaction mixture was then filtered through kieselguhr which was then washed repeatedly with methanol, and the filtrate was concentrated under reduced pressure. The crude product was purified by preparative HPLC (Column: Gromsil, C-18 5 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave the title compound as a colorless solid (34 mg, 26% of theory).

Workup

  1. filtrationThe reaction mixture was then filtered through kieselguhr which
  2. washwas then washed repeatedly with methanol
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe crude product was purified by preparative HPLC (Column

Sources & evidence

ORD record
ord-92c13da4e2ac45f7b1bbd6bf10a4fc30
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

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