Triethylamine → Methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]prop-2-enoate

HRID 1930191ノート

反応式

HRID 1930191 の反応式
CS(Cl)(=O)=O.[C:6]([C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([CH:27]([CH2:32]O)[C:28]([O:30][CH3:31])=[O:29])=[CH:23][C:22]=3[Cl:34])=[C:17]([F:35])[CH:16]=2)[C:12]([CH3:36])=[N:11][C:10]=1[CH3:37])(=[O:8])[NH2:7].C(N(CC)CC)C.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C.O>[C:6]([C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27](=[CH2:32])[C:28]([O:30][CH3:31])=[O:29])=[CH:23][C:22]=3[Cl:34])=[C:17]([F:35])[CH:16]=2)[C:12]([CH3:36])=[N:11][C:10]=1[CH3:37])(=[O:8])[NH2:7]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 59627634Methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]-3-hydroxypropanoate2 回

生成物 1

HCID 59627693Methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]prop-2-enoate収率 40.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

Methanesulfonyl chloride (0.145 L, 1865 mmol) was added over 5 minutes to a stirred solution of methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-2′-fluorobiphenyl-4-yl)-3-hydroxypropanoate (Intermediate 31-8; 488 g, 1065 mmol) and triethylamine (0.520 L, 3730 mmol) in tetrahydrofuran (5.0 L) at 10° C. The reaction was heated to 50° C. and left stirring for 2 hours. The reaction was then cooled to 20° C. The mixture was diluted with ethyl acetate (10.0 L), then water (3.0 L) was added. Saturated aqueous ammonium chloride solution (4.1 L) was added. The organic layer was separated and the aqueous layer extracted with ethyl acetate (2.5 L). The organics were combined, washed with 50% brine/water (5.0 L), dried (magnesium sulphate), filtered and the solvent removed in vacuo. The crude product was dissolved in dichloromethane and then chromatographed on silica (5 Kg of Merck lichro prep silica 15-25 μm, 200 mm diameter column), eluting with a solvent gradient of 0-70% ethylacetate/isohexane. Pure fractions were evaporated to dryness to afford methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]prop-2-enoate (188 g, 40%) as a white solid.

後処理

  1. waitleft
  2. temperatureThe reaction was then cooled to 20° C
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with ethyl acetate (2.5 L)
  5. washwashed with 50% brine/water (5.0 L)
  6. dry with materialdried (magnesium sulphate)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. dissolutionThe crude product was dissolved in dichloromethane
  10. customchromatographed on silica (5 Kg of Merck lichro prep silica 15-25 μm, 200 mm diameter column)
  11. washeluting with a solvent gradient of 0-70% ethylacetate/isohexane
  12. customPure fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-d38a6c64d34b46f98cfa18857d0a5f4b
出典データセット
uspto-grants-2012_05
特許番号
US08188092B2

反応ノート

読み込み中…