Sodium Hydroxide → HCID 178451524, compound

HRID 1751474Notes

Reaction equation

HRID 1751474 reaction equation
[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]

Participants

10

Reactant 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

Product 1

HCID 178451524HCID 178451524, compoundYield 854.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-9c68076f1c744308a5cedbfbbc045329
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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