Pyridine → 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(5-methylpyrazin-2-yl)benzamide

HRID 20521

反応式

HRID 20521 の反応式
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[CH:42]=[CH:41][C:18]([O:19][C:20]3[CH:21]=[C:22]([CH:26]=[C:27]([O:29][C@@H:30]([CH3:40])[CH2:31][O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH:28]=3)[C:23]([OH:25])=O)=[C:17]([F:43])[CH:16]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:44][C:45]1[CH:50]=[N:49][C:48]([CH3:51])=[CH:47][N:46]=1.N1C=CC=CC=1>C(Cl)Cl>[N:9]1([C:13]([C:15]2[CH:42]=[CH:41][C:18]([O:19][C:20]3[CH:21]=[C:22]([CH:26]=[C:27]([O:29][C@@H:30]([CH3:40])[CH2:31][O:32][Si:33]([C:36]([CH3:38])([CH3:39])[CH3:37])([CH3:35])[CH3:34])[CH:28]=3)[C:23]([NH:44][C:45]3[CH:50]=[N:49][C:48]([CH3:51])=[CH:47][N:46]=3)=[O:25])=[C:17]([F:43])[CH:16]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1

参加物

6

反応物 4

HCID 1049PyridineHCID 3132155-Methylpyrazin-2-amineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 593469093-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid

生成物 1

HCID 593468603-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(5-methylpyrazin-2-yl)benzamide収率 101.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.86 g, 6.56 mmol) was added to a solution of 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid (3 g, 5.96 mmol) in DCM (100 mL) and stirred at RT for 11 hour. 2-Amino-5-methylpyrazine (1.3 g, 11.9 mmol) and pyridine (0.94 mL, 11.9 mmol) were added and the reaction stirred for a further 30 mins. The solvent was removed in vacuo. Water (100 mL) was added and the mixture extracted with ethyl acetate (3×50 mL). The extracts were combined and washed with water (1100 mL), brine (100 mL), dried (MgSO4), filtered, and evaporated in vacuo to give the crude product which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (3.6 g).

後処理

  1. stirringthe reaction stirred for a further 30 mins
  2. customThe solvent was removed in vacuo
  3. additionWater (100 mL) was added
  4. extractionthe mixture extracted with ethyl acetate (3×50 mL)
  5. washwashed with water (1100 mL), brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto give the crude product which
  10. customwas chromatographed on silica
  11. washeluting with a gradient of 50-100% ethyl acetate in isohexane

出典と根拠

ORDレコード
ord-96afe686416b477eb7293ac2ceffa2a5
出典データセット
uspto-grants-2010_06
特許番号
US07745475B2

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