Quinoline → (Z)-3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(4-fluoro-phenyl)-vinyl]-pyridin-2-ylmethylthio}-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911500Notes

Reaction equation

HRID 911500 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]#[C:29][C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)=[CH:24][N:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C2C(=CC=CC=2)C=CC=1>[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].CO>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]\[C:30]4[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=4)=[CH:24][N:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 7047QuinolineHCID 667072243-tert-butoxycarbonyl-7-chloro-6-[5-(4-fluorophenylethynyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 66706949(Z)-3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(4-fluoro-phenyl)-vinyl]-pyridin-2-ylmethylthio}-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 63.1%

Reagents, catalysts & solvents 2

HCID 131709914Lindlars catalystCatalystHCID 887MethanolSolvent

Procedure

Dissolve 3-tert-butoxycarbonyl-7-chloro-6-[5-(4-fluorophenylethynyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.0 g, 1.9 mmol), Lindlar catalyst (240 mg), and quinoline (0.8 mL) in methanol (30 mL). Degas, purge with nitrogen, and stir under a balloon of hydrogen for 36 h. Filter the mixture and wash the catalyst with additional methanol. Concentrate the filtrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (8:1) to give (Z)-3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(4-fluoro-phenyl)-vinyl]-pyridin-2-ylmethylthio}-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a clear oil (630 mg, 63%). MS (APCI+) m/z: 525 (M+H), 425 (M+H−Boc)+. Use a method similar to the General Procedure 1-4 to give the title compound as a pale yellow solid. MS (APCI+) m/z: 425 (M+H)+.

Workup

  1. customDegas
  2. custompurge with nitrogen
  3. filtrationFilter the mixture
  4. washwash the catalyst with additional methanol
  5. concentrationConcentrate the filtrate in vacuo
  6. customPurify by chromatography on silica gel eluting with hexane/EtOAc (8:1)

Sources & evidence

ORD record
ord-0c71d037408449519020f403beed8eb0
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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