Sodium Carbonate → HCID 58505685, compound

HRID 1917615Notes

Reaction equation

HRID 1917615 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:18]3[C:13]([CH:14]=[C:15]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH:16]=[CH:17]3)=[C:12]([C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])[C:11]=2[CH2:33][C:34]([CH3:41])([CH3:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:9])=[CH:4][CH:3]=1.[N:42]1[CH:47]=[CH:46][CH:45]=[C:44](B(O)O)[CH:43]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.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>[CH3:29][C:28]([CH3:31])([CH3:30])[C:27]([C:12]1[C:11]([CH2:33][C:34]([CH3:41])([CH3:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[C:10]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:44]3[CH:43]=[N:42][CH:47]=[CH:46][CH:45]=3)=[CH:3][CH:4]=2)=[O:9])[N:18]2[C:13]=1[CH:14]=[C:15]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)[CH:16]=[CH:17]2)=[O:32]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 58505584HCID 58505584, compound

Product 1

HCID 58505685HCID 58505685, compoundYield 65.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

A solution of ethyl 3-{3-[(4-bromophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-(pyridin-2-ylmethoxy)indolizin-2-yl}-2,2-dimethylpropanoate (225 mg, 0.363 mmol), 3-pyridyl boronic acid (89.3, 0.726 mmol), tetrakis(triphenylphosphine)palladium(0) (42.0 mg, 0.036 mmol) in THF (4.0 mL) and aqueous 20% Na2CO3 (2.0 mL) is heated at 70° C. for 24 h then cooled to 23° C. The mixture is partitioned between Et2O and water then the organics are collected, dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, hexanes to EtOAc) gives ethyl 3-[1-(2,2-dimethylpropanoyl)-7-(pyridin-2-ylmethoxy)-3-{[4-(pyridin-3-yl)phenyl]carbonyl}indolizin-2-yl]-2,2-dimethylpropanoate (147 mg, 65%) which is dissolved in THF (1.0 mL), MeOH (1.0 mL), and 6M aqueous NaOH (0.8 mL) and heated at 50° C. for 3 h then cooled to 23° C. and acidified to pH=1 with concentrated aqueous HCl. The mixture is concentrated in vacuo, diluted with DMSO, filtered, and filtrate is purified by HPLC (25% CH3CN to 85% CH3CN in 0.1% TFA in water) to give the title compound (62 mg, 44%).

Workup

  1. customThe mixture is partitioned between Et2O and water
  2. customthe organics are collected
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the crude by flash chromatography (SiO2, hexanes to EtOAc)

Sources & evidence

ORD record
ord-895d84f68c5743a89f0f2dac59cedcac
Source dataset
uspto-grants-2013_12
Patent number
US08618300B2

Reaction notes

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