Sodium Carbonate → HCID 21716778, compound

HRID 1385995Notes

Reaction equation

HRID 1385995 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]2[CH:12]=[CH:11][S:10][CH:9]=2)[CH:7]=1.[C:13]([O:17][C:18]([N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22](B(O)O)=[CH:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C([O-])([O-])=O.[Na+].[Na+]>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>[S:10]1[CH:11]=[CH:12][C:8]([C:6]2[CH:7]=[C:2]([C:22]3[C:23]4[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH:21]=3)[CH:3]=[N:4][CH:5]=2)=[CH:9]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 52330101-(tert-Butoxycarbonyl)indole-3-boronic acidHCID 112764923-Bromo-5-thiophen-3-yl-pyridine

Product 1

HCID 21716778HCID 21716778, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A deoxygenated solution of 3-bromo-5-thiophen-3-yl-pyridine (2.50 g, 10.4 mmol, 1 equiv), 1-(t-butyloxycarbonyl)-3-indoleboronic acid (4.073 g, 15.6 mmol, 1.50 equiv), Pd(PPh3)4 (601 mg, 0.520 mmol, 0.0500 equiv), and 2.0 M Na2CO3 (10.4 mL, 20.8 mmol, 2.00 equiv) in dioxane (120 ml) was heated under argon at reflux for 20 h. The reaction mixture was allowed to cool, then partitioned between water (500 mL) and ethyl acetate (3×150 mL). The combined organic layers were washed sequentially with water (500 mL) and brine (500 ml), then dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (40% ethyl acetate in hexane) to afford 3-(5-thiophen-3-yl-pyridin-3-yl)-1-(t-butyloxycarbonyl)-indole as a colorless oil. The oil was dissolved in ethyl acetate (100 ml), and the resulting solution was cooled to 0° C., then saturated with HCl gas. The solution was allowed to warm to 23° C. and stirred for 30 minutes. The precipitate was filtered and washed with ethyl ether (50 mL). The solid was then partitioned between ethyl acetate (150 mL) and aqueous saturated NaHCO3 solution (150 mL). The organic layer was dried over Na2SO4 and concentrated to give compound 1 (3-(5-thiophen-3-yl-pyridin-3-yl)-indole) as a white solid.

Workup

  1. temperatureat reflux for 20 h
  2. temperatureto cool
  3. custompartitioned between water (500 mL) and ethyl acetate (3×150 mL)
  4. washThe combined organic layers were washed sequentially with water (500 mL) and brine (500 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-18831cab961948f79d2a0e68818c6c77
Source dataset
uspto-grants-2001_07
Patent number
US06265403B1

Reaction notes

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