Dichloromethane → 5-Amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

HRID 1159328ノート

反応式

HRID 1159328 の反応式
Br[C:2]1[N:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.ClCCl.C(N(CC)CC)C.[C]=O.[C:28]([O:31][CH2:32]C)(=[O:30])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CO>[CH3:32][O:31][C:28]([C:2]1[CH:7]=[N:6][C:5]([NH2:8])=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[N:3]=1)=[O:30]

参加物

8

反応物 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 714639895-Bromo-3-(4-fluorophenyl)pyrazin-2-amineHCID 178418416HCID 178418416、化合物

生成物 1

HCID 675046415-Amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 887Methanol溶媒

実験手順

To a methanol solution (35 ml) of 5-bromo-3-(4-fluoro-phenyl)-pyrazin-2-ylamine (1.87 g, 6.97 mmol, 1.0 eq) was added 15 ml ethyl acetate at room temperature. [1,1′-bis(diphenylphosphino) ferrocen]palladium(II)chloride 1:1 complex with dichloromethane (0.26 g, 0.32 mmol, 0.05 eq) was added portion-wise to the reaction mixture followed by triethylamine (1.95 ml, 13.5 mmol, 2.0 eq) and the solution was heated with stirring to 110° C. under 70 bar carbon monoxide for 18 hours. On cooling and removal of carbon monoxide, the reaction mixture was concentrated in vacuo and the residue purified by chromatography on silica gel with heptane:ethyl acetate (1:1) to afford 5-Amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester as white crystals. Yield=1.26 g (73%). 1H-NMR (400 MHz, DMSO): δ 3.80 (3H, s), 7.11 (2H, br s), 7.33 (2H, t, J=8.87 Hz), 7.67-7.70 (2H, m), 8.56 (1H, s). HPLC-MS=100%; 1.49 min (MW=247; M+1=248.3).

後処理

  1. temperaturethe solution was heated
  2. temperatureOn cooling
  3. customremoval of carbon monoxide
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. customthe residue purified by chromatography on silica gel with heptane:ethyl acetate (1:1)

出典と根拠

ORDレコード
ord-05adfe0b66324bf09481ecbd04cda547
出典データセット
uspto-grants-2010_10
特許番号
US07812028B2

反応ノート

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