Potassium Carbonate → HCID 178452523, compound

HRID 1471177Notes

Reaction equation

HRID 1471177 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[N:13]=[C:14]([C@@H:17]3[CH2:22][C@@H:21]4[C@@H:19]([CH2:20]4)[N:18]3[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[NH:15][CH:16]=1)[CH:6]=[CH:5]2.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[NH:48][C:47]([C@@H:49]4[CH2:54][C@@H:53]5[C@@H:51]([CH2:52]5)[N:50]4C(OC(C)(C)C)=O)=[N:46][CH:45]=3)=[CH:40][CH:39]=2)O1.C1(P(C2CCCCC2)[C:70]2C=CC=[CH:72][C:71]=2[C:76]2C(OC)=CC=CC=2OC)CCCCC1.[C:92]([O-:95])([O-:94])=O.[K+].[K+]>C1COCC1.O.CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:71]([O:94][C:92]([N:50]1[C@H:49]([C:47]2[NH:46][CH:45]=[C:44]([C:41]3[CH:42]=[CH:43][C:38]([C:2]4[CH:3]=[C:4]5[C:9](=[CH:10][CH:11]=4)[N:8]=[C:7]([C:12]4[N:13]=[C:14]([C@@H:17]6[CH2:22][C@@H:21]7[C@@H:19]([CH2:20]7)[N:18]6[C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[NH:15][CH:16]=4)[CH:6]=[CH:5]5)=[CH:39][CH:40]=3)[N:48]=2)[CH2:54][C@@H:53]2[C@H:51]1[CH2:52]2)=[O:95])([CH3:76])([CH3:72])[CH3:70]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57816632HCID 57816632, compoundHCID 178452520HCID 178452520, compound

Product 1

HCID 178452523HCID 178452523, compoundYield 303.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

Pd(OAc)2 (7.40 mg, 0.033 mmol) was added to a solution of tert-butyl (1R,3S,5R)-3-(4-(6-bromo-2-quinolinyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (150 mg, 0.329 mmol), (1R,3S,5R)-tert-butyl 3-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (149 mg, 0.329 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (27.0 mg, 0.066 mmol) and K2CO3 (137 mg, 0.988 mmol) in THF (2 mL) and water (0.50 mL) and the reaction mixture was stirred at 110° C. for 2 h. The reaction mixture was diluted with MeOH, filtered and purified by preparative HPLC (H2O-MeOH with 10 mM NH4OAc buffer) to yield tert-butyl(1R,3S,5R)-3-(4-(6-(4-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)phenyl)-2-quinolinyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (140 mg) as bright yellow solid. LC-MS retention time 3.150 min; m/z 700.36 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 5% MeOH/95% H2O/10 mM ammonium acetate and Solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a MICROMASS® Platform for LC in electrospray mode.

Workup

  1. filtrationfiltered
  2. custompurified by preparative HPLC (H2O-MeOH with 10 mM NH4OAc buffer)

Sources & evidence

ORD record
ord-04be924da5f641d5b5516dd9581d870a
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

Loading…