Pyridine → HCID 11713257, 화합물

HRID 1009202

반응식

HRID 1009202 반응식
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

참가 물질

12

반응물 5

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 1371844-(Trifluoromethoxy)benzenemethanolHCID 22371666HCID 22371666, 화합물HCID 67304328HCID 67304328, 화합물

생성물 1

HCID 11713257HCID 11713257, 화합물수율 53.5%

시약·촉매·용매 6

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매HCID 25517Ammonium Chloride용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-7f824038613c45ef80381215ea8660b9
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07973061B2

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