Sodium Hydroxide → HCID 178451524, 화합물

HRID 1751474노트

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HRID 1751474 반응식
[C:1]([O:5][C:6]([N:8]1[CH:13]([C:14](O)=O)[CH2:12][CH:11]2[CH:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:17][C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([NH2:29])[C:24]=2[NH2:28])[CH:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+].[OH-].[Na+]>C(Cl)Cl.CCOC(C)=O.CC(O)=O>[C:1]([O:5][C:6]([N:8]1[CH:13]([C:14]2[NH:28][C:24]3[C:25]4[C:20]([CH:21]=[CH:22][C:23]=3[N:29]=2)=[CH:19][C:18]([Br:17])=[CH:27][CH:26]=4)[CH2:12][CH:11]2[CH:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

10

반응물 6

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 213390052-(Tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acidHCID 220970716-Bromonaphthalene-1,2-diamine

생성물 1

HCID 178451524HCID 178451524, 화합물수율 854.2%

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매2회

실험 절차

To a solution of 2-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester (0.08 g, 0.34 mmol) in CH2Cl2 (3.5 mL) was added 6-Bromo-naphthalene-1,2-diamine (0.09 g, 0.041 mmol), HATU (0.16 g, 0.43 mmol), and DIPEA (0.3 mL, 1.72 mmol). The resulting solution was stirred at room temperature for 1.5 h and diluted with EtOAc. The organic layer was washed with H2O and brine. The aqueous layers were back extracted with EtOAc. The combined organic layers were dried over Na2SO4 and separated. The crude oil was purified by column chromatography (SiO2, 10→100% EtOAc (2% MeOH) in hexanes) to provide an oil that was dissolved in AcOH (7.0 mL). The solution was stirred at 40° C. (external, oil bath) for 2 h. The solution was diluted with EtOAc and slowly basified with saturated sodium bicarbonate and NaOH (2N). The organic layer was separated, dried over Na2SO4, and concentrated. The crude oil was purified by column chromatography (SiO2, 10→100% EtOAc (2% MeOH) in hexanes) to provide 3-(7-Bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (0.15 g, 97%). LCMS-ESI+: calc'd for C21H22BrN3O2: 427.09 (M+); Found: 428.35 (M+H+).

후처리

  1. washThe organic layer was washed with H2O and brine
  2. extractionThe aqueous layers were back extracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. customseparated
  5. customThe crude oil was purified by column chromatography (SiO2, 10→100% EtOAc (2% MeOH) in hexanes)
  6. customto provide an oil that
  7. stirringThe solution was stirred at 40° C. (external, oil bath) for 2 h
  8. customThe organic layer was separated
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe crude oil was purified by column chromatography (SiO2, 10→100% EtOAc (2% MeOH) in hexanes)

출처 및 근거

ORD 기록
ord-9c68076f1c744308a5cedbfbbc045329
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

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