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 2200992ノート

反応式

HRID 2200992 の反応式
[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]

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 27343883-(Trifluoromethyl)phenylboronic acid2 回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

生成物 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

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒2 回HCID 1049Pyridine溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-b122d755f6a742c09fc644169d29294d
出典データセット
uspto-grants-2016_06
特許番号
US09359362B2

反応ノート

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