Sodium Carbonate → N-(3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)methanesulfonamide

HRID 531434Notes

Reaction equation

HRID 531434 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:19]2[CH:20]=[C:21]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)O1.C1(C)C=CC=CC=1.C(O)C.O.C(=O)([O-])[O-].[Na+].[Na+]>CCCCCC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC.O>[NH:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:19]3[CH:20]=[C:21]([NH:25][S:26]([CH3:29])(=[O:27])=[O:28])[CH:22]=[CH:23][CH:24]=3)[CH:3]=[C:4]2[CH:10]=[CH:9]1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridineHCID 162177153-(Methanesulfonylamino)phenylboronic acid pinacol ester2×HCID 86587398Ethanol toluene water

Product 1

HCID 58087575N-(3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)methanesulfonamideYield 57%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×HCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

5-bromo-1H-pyrrolo[2,3-b]pyridine (1 g, 5 mmol) and N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (intermediate 3) (1.6 g, 5 mmol) were added to a solution of toluene/ethanol/water (6/6/5 ml) previously purged with argon (10 min). The reaction mixture was purged with argon for a further 15 mins, followed by the addition of sodium carbonate (1.64 g, 15 mmol) and PdCl2(dppf) (181 mg, 0.2 mmol) and DME/water (10/5 ml). The resulting mixture was heated to reflux at 80° C. overnight. The reaction was monitored by TLC (50% ethylacetate in hexane). The reaction mixture was cooled and diluted with ethyl acetate (50 ml) and washed with water (2×50 ml). The organic layer was dried over Na2SO4, and concentrated under reduced pressure to afford crude product. Purification by column chromatography on silica gel (40% ethyl acetate in hexane) afforded 800 mg (57% yield) MS: m/z=287.9 (M+1).

Workup

  1. custompreviously purged with argon (10 min)
  2. customThe reaction mixture was purged with argon for a further 15 mins
  3. temperatureThe resulting mixture was heated
  4. temperatureThe reaction mixture was cooled
  5. washwashed with water (2×50 ml)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude product
  9. customPurification by column chromatography on silica gel (40% ethyl acetate in hexane)
  10. customafforded 800 mg (57% yield)

Sources & evidence

ORD record
ord-8d66cc779a6b466795a918b1a3265253
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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