Dimethylformamide → HCID 66706916, compound

HRID 911481Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH2:7][S:8][C:9]2[C:19]3[CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15][CH2:14][C:13]=3[CH:12]=[CH:11][C:10]=2[Cl:27])[S:5][CH:6]=1.[CH3:28][N:29](C=O)C>[C-]#N.[Zn+2].[C-]#N>[C:23]([O:22][C:20]([N:16]1[CH2:17][CH2:18][C:19]2[C:9]([S:8][CH2:7][C:4]3[S:5][CH:6]=[C:2]([C:28]#[N:29])[CH:3]=3)=[C:10]([Cl:27])[CH:11]=[CH:12][C:13]=2[CH2:14][CH2:15]1)=[O:21])([CH3:26])([CH3:25])[CH3:24]

Participants

Conditions

Temperature: 120 °C

Procedure

Degas a stirred solution of 6-(4-bromothiophen-2-ylmethylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (183 mg, 0.37 mmol), zinc cyanide (50 mg, 0.42 mmol) and tetrakistriphenylphosphine palladium(0) (30 mg, 0.026 mmol) in dry DMF. Purge with dry nitrogen, and heat at 120° C. for 6 h. Dilute with water, extract three times with EtOAc, dry over anhydrous MgSO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (10:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(4-cyanothiophen-2-ylmethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (85 mg, 52%). MS (APCI+) m/z: 335 (M+H−Boc)+. Use a method similar to the General Procedure 1-4 to give the title compound as a white solid. MS (APCI+) m/z: 335 (M+H)+.

Workup

customPurge with dry nitrogen
additionDilute with water
extractionextract three times with EtOAc
dry with materialdry over anhydrous MgSO4
concentrationconcentrate in vacuo
customPurify by chromatography on silica gel eluting with hexane/EtOAc (10:1)

Sources & evidence

ORD record: ord-42f71acb6c6442e290641ec840f293d7
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022062B2

Reaction notes

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