Potassium Phosphate, Tribasic → HCID 69671794, compound

HRID 1751473Notes

Reaction equation

HRID 1751473 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:13]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22](B4OC(C)(C)C(C)(C)O4)=[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])([CH3:4])([CH3:3])[CH3:2].[C:35]([O:39][C:40]([N:42]1[CH:47]([C:48]2[NH:49][C:50]([C:53]3[CH:58]=[CH:57][C:56](Br)=[CH:55][CH:54]=3)=[CH:51][N:52]=2)[CH2:46][CH:45]2[CH:43]1[CH2:44]2)=[O:41])([CH3:38])([CH3:37])[CH3:36].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.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:1]([O:5][C:6]([N:8]1[CH:13]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:56]4[CH:55]=[CH:54][C:53]([C:50]5[NH:49][C:48]([CH:47]6[CH2:46][CH:45]7[CH:43]([CH2:44]7)[N:42]6[C:40]([O:39][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:41])=[N:52][CH:51]=5)=[CH:58][CH:57]=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])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 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 66981804HCID 66981804, compound

Product 1

HCID 69671794HCID 69671794, compoundYield 62.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

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 (0.19 g, 0.41 mmol) in DME (2.0 mL) was added 3-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (0.16 g, 0.41 mmol), Tetrakis(triphenylphosphine)Palladium (0.05 g, 0.04 mmol) and aqueous potassium phosphate (2 M, 0.60 mL, 1.2 mmol). The solution was degassed with argon for 15 min and heated to 80° C. for 18 h with stirring. The solution was cooled diluted with EtOAc and filtered. The filtrate was washed with H2O and brine. The organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by column chromatography (SiO2, 30→100% EtOAc (10% MeOH) in Hexanes to 80% MeOH in EtOAc). The desired fractions were concentrated and combined with the filtered solid to provide 3-(5-{4′-[2-(2-tert-Butoxycarbonyl-2-aza-bicyclo[3.1.0]hex-3-yl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-imidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (0.17 g, 62%). LCMS-ESI+: calc'd for C39H46N6O4: 662.36 (M+); Found: 663.39 (M+H+).

Workup

  1. customThe solution was degassed with argon for 15 min
  2. temperatureThe solution was cooled
  3. additiondiluted with EtOAc
  4. filtrationfiltered
  5. washThe filtrate was washed with H2O and brine
  6. dry with materialThe organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude oil was purified by column chromatography (SiO2, 30→100% EtOAc (10% MeOH) in Hexanes to 80% MeOH in EtOAc)
  9. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-531a63124d1347e68f4a0d0d9d87d9f5
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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