Pyridine → HCID 11713257, compound

HRID 1009202

Reaction equation

HRID 1009202 reaction equation
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

Participants

12

Reactant 5

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 1371844-(Trifluoromethoxy)benzenemethanolHCID 22371666HCID 22371666, compoundHCID 67304328HCID 67304328, compound

Product 1

HCID 11713257HCID 11713257, compoundYield 53.5%

Reagents, catalysts & solvents 6

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-7f824038613c45ef80381215ea8660b9
Source dataset
uspto-grants-2011_07
Patent number
US07973061B2

Linked notes

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