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Dimethylformamide → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-cyano-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353876
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HRID 2353876 반응식
[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([N:14]([C:30](=[O:32])[CH3:31])[CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[C:9]2[CH:33]=[CH:34][C:35](Br)=[CH:36][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[CH3:38][N:39](C)C=O>C(OCC)(=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:30]([N:14]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=1)[CH:10]1[CH2:11][CH2:12][CH2:13][N:7]([C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:6])[C:8]2[CH:36]=[C:35]([C:38]#[N:39])[CH:34]=[CH:33][C:9]1=2)(=[O:32])[CH3:31]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 2

HCID 6228DimethylformamideHCID 59003154Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

생성물 1

HCID 86616065Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-cyano-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate수율 51%

시약·촉매·용매 4

HCID 23994Zinc촉매2회
HCID 9811564
Bis(dibenzylideneacetone)palladium
촉매
HCID 11979704Tetrakis(triphenylphosphine)palladium촉매
HCID 8857Ethyl Acetate용매

실험 절차

Purge with nitrogen, a solution of isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.074 g, 0.124 mmol) and zinc cyamide (0.014 g, 0.124 mmol) in N,N-dimethylformamide (2 mL) in a 10 mL microwave vial. Add tetrakis(triphenylphosphine)palladium (0) (0.0043 g, 0.0037 mmol) and irradiate the mixture at 175° C. for 0.5 h (60-80 Watts). Add a second portion of zinc cyamide (0.014 g, 0.124 mmol) and tetrakis(triphenylphosphine) palladium (0) (0.0043 g, 0.0037 mmol) and continue irradiating for 8 min. Cool the mixture to room temperature and dilute with ethyl acetate (35 mL) and wash with water (3×25 mL) and brine (25 mL each), then dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as a crushable white foam (0.034 g, 51%): ESI MS 542 (M+H).

후처리

  1. customPurge with nitrogen
  2. customcontinue irradiating for 8 min
  3. washwash with water (3×25 mL) and brine (25 mL each)
  4. dry with materialdry the organic layer over sodium sulfate
  5. filtrationfilter
  6. customremove the solvent under reduced pressure
  7. customPurify the residue
  8. washeluting with hexanes/ethyl acetate (60:40)

출처 및 근거

ORD 기록
ord-464f9ca239094c4d95223b791f0c87fe
출처 데이터셋
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07749992B2

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