Triethylamine → tert-butyl (1E,4E)-8-bromo-4-((3-fluoropropyl)(propyl)carbamoyl)-3H-benzo[b]azepin-2-ylcarbamate

HRID 593468Notes

Reaction equation

HRID 593468 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:23]=1)[N:7]=[C:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C:10]([C:12](O)=[O:13])=[CH:11]2.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[F:46][CH2:47][CH2:48][CH2:49][NH:50][CH2:51][CH2:52][CH3:53].C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:23]=1)[N:7]=[C:8]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])[CH2:9][C:10]([C:12](=[O:13])[N:50]([CH2:49][CH2:48][CH2:47][F:46])[CH2:51][CH2:52][CH3:53])=[CH:11]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 669596238-bromo-2-((tert-butoxycarbonyl)amino)-3H-benzo[b]azepine-4-carboxylic acidHCID 866534873-Fluoro-N-propylpropan-1-amine hydrochloride

Product 1

HCID 86653486tert-butyl (1E,4E)-8-bromo-4-((3-fluoropropyl)(propyl)carbamoyl)-3H-benzo[b]azepin-2-ylcarbamateYield 148.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1E,4E)-8-Bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylic acid (0.275 g, 0.721 mmol) was dissolved in 7 mls of dry DMF. To this solution was added HOBT (0.107 g, 0.794 mmol) and EDCI (0.152 mmol, 0.794 mmol), and this mixture was stirred at room temperature for 20 minutes. 3-Fluoro-N-propylpropan-1-amine hydrochloride (0.124 mmol, 0.794 mmol) followed by triethylamine (0.211 mls, 1.515 mmol) were then added and the reaction mixture stirred at room temperature for 16 hours. The mixture was then diluted with EtOAc, washed several times with brine, dried over sodium sulfate and concentrated under reduced pressure. Flash 40 Biotage (40S cartridge, 25% EtOAc/Hexane) afforded 0.089 g (26%) of tert-butyl (1E,4E)-8-bromo-4-((3-fluoropropyl)(propyl)carbamoyl)-3H-benzo[b]azepin-2-ylcarbamate. m/z (APCI-pos) M+1=481.8 and 483.8.

Workup

  1. additionwere then added
  2. stirringthe reaction mixture stirred at room temperature for 16 hours
  3. washwashed several times with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d6fb43f1e7f94294911db8fb5bdcd3dc
Source dataset
uspto-grants-2016_01
Patent number
US09242964B2

Reaction notes

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