Sodium Bicarbonate → 2-(5-{7-[2-(1-Boc-pyrrolidin-2-yl)-3H-imidazol-4-yl]-9,10-dihydro-phenanthren-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1185615Notes

Reaction equation

HRID 1185615 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:22]=[CH:21][C:20]3[C:19]4[C:14](=[CH:15][C:16](B5OC(C)(C)C(C)(C)O5)=[CH:17][CH:18]=4)[CH2:13][CH2:12][C:11]=3[CH:10]=2)O1.[C:33]([O:37][C:38]([N:40]1[CH2:44][CH2:43][CH2:42][CH:41]1[C:45]1[NH:46][CH:47]=[C:48](Br)[N:49]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34].[C:51]([O-:54])(O)=[O:52].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:33]([O:37][C:38]([N:40]1[CH2:44][CH2:43][CH2:42][CH:41]1[C:45]1[NH:49][C:48]([C:9]2[CH:10]=[CH:11][C:20]3[C:19]4[C:14](=[CH:15][C:16]([C:48]5[NH:49][C:45]([CH:41]6[CH2:42][CH2:43][CH2:44][N:40]6[C:51]([O:54][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:52])=[N:46][CH:47]=5)=[CH:17][CH:18]=4)[CH2:13][CH2:12][C:21]=3[CH:22]=2)=[CH:47][N:46]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 587894764,4,5,5-Tetramethyl-2-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-9,10-dihydro-phenanthren-2-yl]-[1,3,2]dioxaborolaneHCID 178451675HCID 178451675, compound

Product 1

HCID 666212102-(5-{7-[2-(1-Boc-pyrrolidin-2-yl)-3H-imidazol-4-yl]-9,10-dihydro-phenanthren-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 24%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd(PPh3)4 (31 mg, 0.03 mmol) was added to a mixture 4,4,5,5-tetramethyl-2-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-9,10-dihydro-phenanthren-2-yl]-[1,3,2]dioxaborolane (115 mg, 0.27 mmol), 2-(4-bromo-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (173 mg, 0.55 mmol), NaHCO3 (159 mg, 1.9 mmol) in 1,2-dimethoxyethane (5 mL) and water (1 mL). The reaction mixture was flushed with nitrogen, heated at 80° C. for 6 hours, and then the volatile component was removed in vacuo. The residue was dissolved in ethyl acetate (100 mL), washed with NaHCO3 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 as a white solid (42 mg, 24%). m/z 651.0 (M+H)+.

Workup

  1. customThe reaction mixture was flushed with nitrogen
  2. customthe volatile component was removed in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  4. washwashed with NaHCO3 solution, water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe obtained residue was purified by flash chromatography

Sources & evidence

ORD record
ord-b7b54e6c001d4c3da01333fe32a017e0
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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