Cesium carbonate → HCID 71090349, compound

HRID 331063Notes

Reaction equation

HRID 331063 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:22])[CH:9]=[C:10]([C:11]3[CH:19]=[C:18]4[C:14]([CH2:15][CH:16]([CH3:21])[N:17]4[CH3:20])=[CH:13][CH:12]=3)[C:3]=12.[CH3:23][N:24]1[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:31])=[O:30])=[N:25]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:20][N:17]1[C:18]2[C:14](=[CH:13][CH:12]=[C:11]([C:10]3[C:3]4[C:4](=[N:5][CH:6]=[CH:7][C:2]=4[NH:32][S:29]([C:26]4[CH:27]=[CH:28][N:24]([CH3:23])[N:25]=4)(=[O:31])=[O:30])[N:8]([CH3:22])[CH:9]=3)[CH:19]=2)[CH2:15][CH:16]1[CH3:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 148356431-methyl-1H-pyrazole-3-sulfonamideHCID 711145544-bromo-3-(1,2-dimethylindolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 71090349HCID 71090349, compoundYield 30.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

4-Bromo-3-(1,2-dimethylindolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine (541 mg, 1.519 mmol), 1-methyl-1H-pyrazole-3-sulfonamide (D94) (367 mg, 2.278 mmol), Pd2(dba)3 (139 mg, 0.152 mmol), xantphos (176 mg, 0.304 mmol) and cesium carbonate (1484 mg, 4.56 mmol) charged into a microwave vial and suspended in 1,4-dioxane (8.0 mL). The reaction mixture was degassed under nitrogen for 10 mins before subjected to microwave heating at 120° C. for 30 mins. The reaction mixture was then partitioned between ethyl acetate/water (ca. 30 mL each). Aqueous layer was separated and re-extracted with ethyl acetate (ca. 25 mL twice). The combined organic layers were dried over MgSO4 and solvent removed in vacuo. The residue was purified using chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in cyclohexane and followed by another purification on silica, eluting with a gradient of 0-40% ethyl acetate in DCM to afford title compound (205 mg). LCMS (A): m/z (M+H)+ 437, C22H24N6O2S requires 436 (acidic).

Workup

  1. customThe reaction mixture was degassed under nitrogen for 10 mins
  2. customThe reaction mixture was then partitioned between ethyl acetate/water (ca. 30 mL each)
  3. customAqueous layer was separated
  4. extractionre-extracted with ethyl acetate (ca. 25 mL twice)
  5. dry with materialThe combined organic layers were dried over MgSO4 and solvent
  6. customremoved in vacuo
  7. customThe residue was purified
  8. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane
  9. customfollowed by another purification on silica
  10. washeluting with a gradient of 0-40% ethyl acetate in DCM

Sources & evidence

ORD record
ord-6054ea0abf394fbab4f91defac071583
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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