Dimethylformamide → HCID 66706916, compound

HRID 2041357Notes

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-a9cd7422840c45d4a7e0b8e70e8d01cf
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580780B2

Reaction notes

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