Water → HCID 58505750, compound

HRID 1917621Notes

Reaction equation

HRID 1917621 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[N:19]3[C:14]([CH:15]=[C:16]([CH:20]([CH3:22])[CH3:21])[CH:17]=[CH:18]3)=[C:13]([C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[C:12]=2[CH2:29][C:30]([CH3:37])([CH3:36])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:10])=[CH:4][CH:3]=1.[CH3:38][O:39][C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][N:41]=1.O>O1CCOCC1.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>[CH3:25][C:24]([CH3:27])([CH3:26])[C:23]([C:13]1[C:12]([CH2:29][C:30]([CH3:37])([CH3:36])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:11]([C:9](=[O:10])[NH:8][C:5]2[CH:6]=[CH:7][C:2]([C:43]3[CH:42]=[N:41][C:40]([O:39][CH3:38])=[CH:45][CH:44]=3)=[CH:3][CH:4]=2)[N:19]2[C:14]=1[CH:15]=[C:16]([CH:20]([CH3:22])[CH3:21])[CH:17]=[CH:18]2)=[O:28]

Participants

6

Reactant 3

HCID 962WaterHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 58505583HCID 58505583, compound

Product 1

HCID 58505750HCID 58505750, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
23 °C

Procedure

A solution of ethyl 3-{3-[(4-bromophenyl)carbamoyl]-1-(2,2-dimethylpropanoyl)-7-(propan-2-yl)indolizin-2-yl}-2,2-dimethylpropanoate (55 mg, 0.097 mmol), 2-(methoxy)pyridine-5-boronic acid (15 mg, 0.097 mmol) and tetrakis(triphenylphosphine)palladium (0) (5 mg, 0.007 mmol) in 1,4-dioxane (4 mL) is heated in the microwave at 120° C. for 20 minutes then 100° C. for 16 h. The mixture is cooled to 23° C., poured into water and extracted with EtOAc. The combined organics are dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, hexanes to 50% EtOAc in hexanes) gives ethyl 3-[1-(2,2-dimethylpropanoyl)-3-{[4-(6-methoxypyridin-3-yl)phenyl]carbamoyl}-7-(propan-2-yl)indolizin-2-yl]-2,2-dimethylpropanoate (22 mg, 38%) that is dissolved in 1,4-dioxane (3 mL) and water (0.5 mL). To this mixture is added 10M aqueous NaOH (5 drops) and solution is stirred at 23° C. until reaction is complete. The mixture is acidified with HOAc and resulting solid is filtered, washed with water, collected, and dried to give the title compound (14 mg, 67%).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organics are dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude by flash chromatography (SiO2, hexanes to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c7ffab3ed19347a7bc64b263664e270c
Source dataset
uspto-grants-2013_12
Patent number
US08618300B2

Reaction notes

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