Sodium Carbonate → HCID 58505677, compound

HRID 1917616Notes

Reaction equation

HRID 1917616 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]([CH:19]([CH3:21])[CH3:20])[CH:16]=[CH:17]3)=[C:12]([C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24])[C:11]=2[CH2:28][C:29]([CH3:35])([CH3:34])[C:30]([O:32][CH3:33])=[O:31])=[O:9])=[CH:4][CH:3]=1.[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][N:39]=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>[CH3:24][C:23]([CH3:25])([CH3:26])[C:22]([C:12]1[C:11]([CH2:28][C:29]([CH3:34])([CH3:35])[C:30]([O:32][CH3:33])=[O:31])=[C:10]([C:8]([C:5]2[CH:6]=[CH:7][CH:2]=[C:3]([C:41]3[CH:40]=[N:39][C:38]([O:37][CH3:36])=[CH:43][CH:42]=3)[CH:4]=2)=[O:9])[N:18]2[C:13]=1[CH:14]=[C:15]([CH:19]([CH3:20])[CH3:21])[CH:16]=[CH:17]2)=[O:27]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 58505652HCID 58505652, compound

Product 1

HCID 58505677HCID 58505677, compoundYield 88.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

A solution of methyl 3-{3-[(4-bromophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-(propan-2-yl)indolizin-2-yl}-2,2-dimethylpropanoate (100 mg, 0.185 mmol), 2-(methoxy)pyridine-5-boronic acid (42.5 mg, 0.278 mmol), tetrakis(triphenylphosphine)palladium(0) (21.4 mg, 0.019 mmol) in THF (2.0 mL) and aqueous 20% Na2CO3 (1.0 mL) is heated at 70° C. for 1 h. The mixture is cooled to 23° C. and partitioned between Et2O and water. The organics are collected, dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, hexanes to 30% EtOAc in hexanes) gives methyl 3-[1-(2,2-dimethylpropanoyl)-3-{[3-(6-methoxypyridin-3-yl)phenyl]carbonyl}-7-(propan-2-yl)indolizin-2-yl]-2,2-dimethylpropanoate (93 mg, 88%) which is dissolved in MeOH (1.5 mL), and 6M aqueous NaOH (1.5 mL) and heated at 70° C. for 1 h. The mixture is then cooled to 23° C., acidified to pH=1 with concentrated aqueous HCl, and partitioned between CH2Cl2 and brine. The organics are collected, dried with MgSO4, filtered, and concentrated in vacuo to give the title compound (68 mg, 75%).

Workup

  1. custompartitioned 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 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6fdfbe23c9fb411ea9ecfce0eb4c45b1
Source dataset
uspto-grants-2013_12
Patent number
US08618300B2

Reaction notes

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