Dichloromethane → (rac)-7-(4-Cyanophenyl)-5-methyl-2-thiophen-2-yl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile

HRID 2200992Notes

Reaction equation

HRID 2200992 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]3[N:15]=[C:16]([C:18]4[S:19][CH:20]=[CH:21][CH:22]=4)[N:17]=[C:13]3[NH:12][C:11]([CH3:23])=[C:10]2[C:24]#[N:25])=[CH:5][CH:4]=1)#[N:2].ClCCl.[F:29][C:30]([F:41])([F:40])[C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.N1C=CC=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]3[N:15]=[C:16]([C:18]4[S:19][CH:20]=[CH:21][CH:22]=4)[N:17]=[C:13]3[N:12]([C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([C:30]([F:41])([F:40])[F:29])[CH:36]=3)[C:11]([CH3:23])=[C:10]2[C:24]#[N:25])=[CH:5][CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 27343883-(Trifluoromethyl)phenylboronic acid2×HCID 136355665(rac)-7-(4-Cyanophenyl)-5-methyl-2-thiophen-2-yl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile

Product 1

HCID 46841489(rac)-7-(4-Cyanophenyl)-5-methyl-2-thiophen-2-yl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 1049PyridineSolvent2×

Procedure

Under an atmosphere of argon protective gas, (rac)-7-(4-cyanophenyl)-5-methyl-2-thiophen-2-yl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (70 mg, 230 μmol) was stirred in abs. dichloromethane (60 ml) with molecular sieve (0.5 g, 4 Å) for 1 h. 3-(Trifluoromethyl)phenylboronic acid (131 mg, 690 μmol, 3 eq.), anhydrous copper(II) acetate (125 mg, 690 μmol, 3 eq.), abs. pyridine (1668 μl) and triethylamine (70 mg, 690 μmol, 3 eq.) were then added, and the mixture was stirred at RT for 12 h. More molecular sieve (0.5 g, 4 Å), 3-(trifluoromethyl)phenylboronic acid (44 mg, 230 μmol, 1 eq.), anhydrous copper(II) acetate (42 mg, 230 μmol, 1 eq.) and abs. pyridine (500 μl) were then added, and the mixture was stirred at RT for a further 3 d. The reaction mixture was then filtered through kieselguhr, the filter residue was washed with dichloromethane and pyridine and the filtrate was concentrated to dryness. The residue was purified by preparative HPLC (Gromsil C18 column, 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). The product was obtained as a colorless solid (40.1 mg, 36% of theory).

Workup

  1. stirringthe mixture was stirred at RT for a further 3 d
  2. filtrationThe reaction mixture was then filtered through kieselguhr
  3. washthe filter residue was washed with dichloromethane and pyridine
  4. concentrationthe filtrate was concentrated to dryness
  5. customThe residue was purified by preparative HPLC (Gromsil C18 column, 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)
  6. customThe product was obtained as a colorless solid (40.1 mg, 36% of theory)

Sources & evidence

ORD record
ord-b122d755f6a742c09fc644169d29294d
Source dataset
uspto-grants-2016_06
Patent number
US09359362B2

Reaction notes

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