Potassium Carbonate → HCID 11610536, compound

HRID 1445858Notes

Reaction equation

HRID 1445858 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][O:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:27]=1.Br[C:38]1[CH:43]=[CH:42][C:41]([C:44]2[O:45][C:46]([CH3:57])=[C:47]([CH2:49][CH2:50][N:51]3[CH2:55][CH2:54][CH2:53][C@H:52]3[CH3:56])[N:48]=2)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)C>[CH3:20][O:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26]([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[O:45][C:46]([CH3:57])=[C:47]([CH2:49][CH2:50][N:51]4[CH2:55][CH2:54][CH2:53][C@H:52]4[CH3:56])[N:48]=3)=[CH:40][CH:39]=2)[CH:27]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 38661613-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 11530378HCID 11530378, compound

Product 1

HCID 11610536HCID 11610536, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of palladium (II) acetate (0.004 g, 0.02 mmol) in anhydrous toluene (5 mL), add triphenylphosphine (0.019 g, 0.07 mmol), under nitrogen and at room temperature. Stir for 15 minutes then add distilled water (1.5 mL), ethanol (1 mL), 3-methoxypyridine-5-boronic acid pinacol ester (0.26 g, 1.10 mmol), 2-(4-bromophenyl)-4-{2-[(2R)-2-methylpyrrolidin-1-yl]ethyl}-5-methyl-1,3-oxazole (See Intermediate 73(0.32 g, 0.92 mmol) and potassium carbonate (0.38 g, 2.75 mmol). Heat the reaction mixture at 110° C. overnight. Cool to room temperature then pour into water. Extract with dichloromethane then concentrate the combined extracts in vacuo. Load onto a 10 g Isolute® SCX-2 column (preconditioned with methanol). Wash the SCX-2 with methanol then elute the target compound with 2N ammonia in methanol solution followed by 7N ammonia in methanol. Concentrate the combined ammonia solutions in vacuo to give a pale yellow solid (0.16 g). Purify using automated flash chromatography (ISCO® System, 12 g Redisep® SiO2 column; 0-30% methanol in ethyl acetate gradient elution over 20 minutes at 30 mL/min) to give the title compound as a pale yellow solid (0.23 g): MS (m/e): 378(M+1).

Workup

  1. customat room temperature
  2. additionthen add
  3. temperatureCool to room temperature
  4. extractionExtract with dichloromethane
  5. concentrationthen concentrate the combined extracts in vacuo
  6. washWash the SCX-2 with methanol
  7. washthen elute the target compound with 2N ammonia in methanol solution
  8. concentrationConcentrate the combined ammonia solutions in vacuo

Sources & evidence

ORD record
ord-844865cbbe4447c28e94014fd02b6a5c
Source dataset
uspto-grants-2010_02
Patent number
US07666871B2

Reaction notes

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