Triethylamine → HCID 66706886, compound

HRID 911732Notes

Reaction equation

HRID 911732 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([SH:20])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:28]([C:30]1[CH:31]=[C:32]([CH:43]=[CH:44][CH:45]=1)[C:33]([C:35]1[CH:42]=[CH:41][C:38]([CH2:39]Br)=[CH:37][CH:36]=1)=[O:34])#[N:29]>CS(C)=O.CCCCCC.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:39][C:38]3[CH:37]=[CH:36][C:35]([C:33](=[O:34])[C:32]4[CH:43]=[CH:44][CH:45]=[C:30]([C:28]#[N:29])[CH:31]=4)=[CH:42][CH:41]=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

6

Reactant 3

HCID 8471TriethylamineHCID 57656151HCID 57656151, compoundHCID 66706900HCID 66706900, compound

Product 1

HCID 66706886HCID 66706886, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
40 °C

Procedure

Dissolve 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (200 mg, 0.52 mmol) in methanol (12 mL) and add potassium hydroxide (0.935 g, 16.66 mmol). Heat at 60° C. for 4 h Cool the reaction mixture to ambient temperature, add aqueous saturated ammonium chloride and concentrate in vacuo. Partition the residue between EtOAc and water. Dry the organic phase over anhydrous Na2SO4 and concentrate in vacuo to give 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.16 g, 5.2 mmol). Dissolve the crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.16 g, 0.52 mmol) in anhydrous DMSO (5 mL) and add triethylamine (0.435 mL, 3.12 mmol) and 4-(3-cyano-benzoyl)benzyl bromide (289 mg, 0.96 mmol). Heat the solution at 40° C. overnight. Cool to ambient temperature, dilute the mixture with hexane/EtOAc (1:1, 100 mL), and wash the organic solution sequentially with brine and ice-cold water. Dry the organic layer over anhydrous Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (9:1, 4:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[4-(3-cyanobenzoyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as oil (212 mg, 77%).

Workup

  1. temperatureCool to ambient temperature
  2. washwash the organic solution sequentially with brine and ice-cold water
  3. dry with materialDry the organic layer over anhydrous Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (9:1, 4:1)

Sources & evidence

ORD record
ord-31209b7c428c435f932a15c3185bd5d1
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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