Pyridine → HCID 11713257、化合物

HRID 1009202

反応式

HRID 1009202 の反応式
C1C([N+]([O-])=O)=CC=C([Cl-][C:11]([O-])=[O:12])C=1.[F:14][C:15]([F:26])([F:25])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][OH:22])=[CH:19][CH:18]=1.N1C=CC=CC=1.[N+](C1C=CC(NC(=O)[O-])=CC=1)([O-])=O.Cl.[Cl:47][C:48]1[CH:49]=[C:50]([CH2:54][CH2:55][NH:56][C:57]([C:59]2[N:60]=[C:61]([CH2:64][NH2:65])[S:62][CH:63]=2)=[O:58])[CH:51]=[CH:52][CH:53]=1.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.[Cl-].[NH4+].CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl>[F:14][C:15]([F:25])([F:26])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][O:22][C:11](=[O:12])[NH:65][CH2:64][C:61]2[S:62][CH:63]=[C:59]([C:57](=[O:58])[NH:56][CH2:55][CH2:54][C:50]3[CH:51]=[CH:52][CH:53]=[C:48]([Cl:47])[CH:49]=3)[N:60]=2)=[CH:19][CH:18]=1

参加物

12

反応物 5

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 1371844-(Trifluoromethoxy)benzenemethanolHCID 22371666HCID 22371666、化合物HCID 67304328HCID 67304328、化合物

生成物 1

HCID 11713257HCID 11713257、化合物収率 53.5%

試薬・触媒・溶媒 6

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 25517Ammonium Chloride溶媒

実験手順

4-Nitrophenylchloroformate (0.1 g, 0.5 mmol) was added to a stirring solution of 4-(trifluoromethoxy)benzyl alcohol (0.09 g, 0.5 mmol), pyridine (0.07 mL, 0.9 mmol), and methylene chloride (2 mL). DMAP (6 mg) was added and the mixture was stirred for 12 hours. The mixture was diluted with saturated ammonium chloride and extracted 3× with methylene chloride. The combined organic layers were washed with 0.5 N NaHSO4 and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (EtOAc/hexane). The 4-nitrophenylcarbamate was mixed with 2-aminomethyl-thiazole-4-carboxylic acid [2-(3-chlorophenyl)ethyl]amide hydrochloride (0.14 g, 0.4 mmol) and DIEA (0.2 mL) in DMF (5 mL). The mixture was stirred for 12 hours. The mixture was diluted EtOAc and water. The layers were separated and the aqueous layer was extracted with 3×EtOAc. The combined organic layers were washed with 5% aqueous lithium chloride and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The material was purified by flash chromatography (EtOAc/hexane) to afford the title compound (0.11 g, 50%): 1H NMR (400 MHz, d6-DMSO): 8.42 (t, 1H), 8.30 (t, 1H), 8.11 (s, 1H), 7.48 (d, 2H), 7.36 (d, 2H), 7.27 (m, 3H), 7.17 (d, 1H), 5.11 (s, 2H), 4.49 (d, 2H), 3.48 (m, 2H), 2.84 (t, 2H); MS (ESI-LCMS) for C22H20ClF3N3O4S: 514 (MH+).

後処理

  1. extractionextracted 3× with methylene chloride
  2. washThe combined organic layers were washed with 0.5 N NaHSO4 and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (EtOAc/hexane)
  7. stirringThe mixture was stirred for 12 hours
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with 3×EtOAc
  10. washThe combined organic layers were washed with 5% aqueous lithium chloride and brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe material was purified by flash chromatography (EtOAc/hexane)

出典と根拠

ORDレコード
ord-7f824038613c45ef80381215ea8660b9
出典データセット
uspto-grants-2011_07
特許番号
US07973061B2

関連ノート

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