Hydrochloric Acid → HCID 69675391, compound

HRID 1751469Notes

Reaction equation

HRID 1751469 reaction equation
C(O[C:6]([N:8]1[CH:13]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22]([B:25]4[O:29][C:28]([CH3:31])([CH3:30])[C:27]([CH3:33])([CH3:32])[O:26]4)=[CH:21][CH:20]=3)=[CH:17][N:18]=2)[CH:12]2[CH2:34][CH:9]1[CH2:10][CH2:11]2)=[O:7])(C)(C)C.Cl.[CH3:36][O:37][C:38]([NH:40][CH:41]([CH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1)C(O)=O)=[O:39].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CO.CCOC(C)=O>[CH3:36][O:37][C:38](=[O:39])[NH:40][CH:41]([CH:45]1[CH2:46][CH2:47][O:48][CH2:49][CH2:50]1)[C:6](=[O:7])[N:8]1[CH:13]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22]([B:25]4[O:29][C:28]([CH3:30])([CH3:31])[C:27]([CH3:32])([CH3:33])[O:26]4)=[CH:21][CH:20]=3)=[CH:17][N:18]=2)[CH:12]2[CH2:34][CH:9]1[CH2:10][CH2:11]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 585162412-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 666205563-{5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-2-azabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl esterHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

Product 1

HCID 69675391HCID 69675391, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-{5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (0.25 g, 0.54 mmol) in CH2Cl2 (5 mL) and MeOH (0.5 mL) was added HCl (in dioxane, 4 M, 1.35 mL, 5.40 mmol). The solution was stirred at room temperature for 2 h and concentrated to dryness. The resulting solid was slurried in CH2Cl2 (5 mL) and DMF (1 mL). Methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (0.15 g, 0.71 mmol), COMU (0.25 g, 0.59 mmol), and DIPEA (0.50 mL, 0.59 mmol) were added, and the resulting solution was stirred at room temperature for 1 h. The reaction was diluted with EtOAc and washed with saturated sodium bicarbonate and brine. The aqueous layers were back extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by column chromatography (SiO2, 10→100% EtOAc (10% MeOH) in Hexanes) to provide [2-Oxo-1-(tetrahydro-pyran-4-yl)-2-(3-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]hept-2-yl)-ethyl]-carbamic acid methyl ester (0.24 g, 79%). LCMS-ESI+: calc'd for C30H41BN4O6: 564.31 (M+); Found: 565.40 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. stirringthe resulting solution was stirred at room temperature for 1 h
  3. washwashed with saturated sodium bicarbonate and brine
  4. extractionThe aqueous layers were back extracted with EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude oil was purified by column chromatography (SiO2, 10→100% EtOAc (10% MeOH) in Hexanes)

Sources & evidence

ORD record
ord-2232debd783945e3b764e008bea1baf0
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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