Hydrochloric Acid → (1-{2-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 417592Notes

Reaction equation

HRID 417592 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:31]=[CH:30][C:29]3[C:28]4[C:23](=[CH:24][C:25]([Br:32])=[CH:26][CH:27]=4)[CH2:22][CH2:21][C:20]=3[CH:19]=2)=[CH:16][N:17]=1)=O)(C)(C)C.Cl.[CH3:34][O:35][C:36]([NH:38][CH:39]([CH:43]([CH3:45])[CH3:44])[C:40](O)=[O:41])=[O:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CO.O1CCOCC1.CCOCC>[CH3:34][O:35][C:36](=[O:37])[NH:38][CH:39]([C:40]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:31]=[CH:30][C:29]3[C:28]4[C:23](=[CH:24][C:25]([Br:32])=[CH:26][CH:27]=4)[CH2:22][CH2:21][C:20]=3[CH:19]=2)=[CH:16][N:17]=1)=[O:41])[CH:43]([CH3:45])[CH3:44]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 666209942-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66620391(1-{2-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 95.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (187 mg, 0.38 mmol) in methanol (5 mL) was added 4.0 M solution of HCl in dioxane (2 mL, excess). The mixture was stirred for 3 hours at 50° C. and concentated under reduced pressure. The residue was treated with ether to remove excess HCl. The obtained white solid was dissoved in DMF (5 mL), to the solution was added 2-methoxycarbonylamino-3-methyl-butyric acid (70 mg, 0.40 mmol), HATU (173 mg, 0.46 mmol) and N,N-diisopropylethylamine (0.66 mL, 3.8 mmol). The mixture was stirred at ambient for 2 hours, and then the volatile component was removed in vacuo. The residue was dissolved in ethyl acetate (100 mL), washed with 1 N NaOH solution, water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product (1-{2-[5-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester as an oil (200 mg, 95%). m/z 551.2, 553.2 (M+H)+.

Workup

  1. customto remove excess HCl
  2. stirringThe mixture was stirred at ambient for 2 hours
  3. customthe volatile component was removed in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  5. washwashed with 1 N NaOH solution, water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe obtained residue was purified by flash chromatography

Sources & evidence

ORD record
ord-3f3048b92e0d4fe086fb94f0bd289929
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Reaction notes

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