Pyridine → HCID 66602261, compound

HRID 707592Notes

Reaction equation

HRID 707592 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].[C:33]([C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)#[N:34].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:38]2[CH:39]=[CH:40][C:35]([C:33]#[N:34])=[CH:36][CH:37]=2)=[C:5]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 27343264-Cyanophenylboronic 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 66602261HCID 66602261, compoundYield 20.5%

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), 4-cyanophenylboronic acid (127.7 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 4 days. The reaction mixture was then filtered through kieselguhr which was then repeatedly washed 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→80:20). This gave the title compound as a colorless solid (25 mg, 19.5% of theory).

Workup

  1. filtrationThe reaction mixture was then filtered through kieselguhr which
  2. washwas then repeatedly washed 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-d94902398293434f9b4608e9d9b32f19
Source dataset
uspto-grants-2015_11
Patent number
US09174997B2

Reaction notes

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