Cesium carbonate → N-(1,6-dimethyl-3-(3-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methyl-1H-pyrazole-3-sulfonamide

HRID 331058Notes

Reaction equation

HRID 331058 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([S:7]([NH2:10])(=[O:9])=[O:8])=[N:3]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+].Cl[C:60]1[CH:65]=[C:64]([CH3:66])[N:63]=[C:62]2[N:67]([CH3:81])[CH:68]=[C:69]([C:70]3[CH:75]=[CH:74][CH:73]=[C:72]([N:76]4[CH2:80][CH2:79][CH2:78][CH2:77]4)[CH:71]=3)[C:61]=12>O1CCOCC1.CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:81][N:67]1[C:62]2=[N:63][C:64]([CH3:66])=[CH:65][C:60]([NH:10][S:7]([C:4]3[CH:5]=[CH:6][N:2]([CH3:1])[N:3]=3)(=[O:9])=[O:8])=[C:61]2[C:69]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([N:76]3[CH2:80][CH2:79][CH2:78][CH2:77]3)[CH:71]=2)=[CH:68]1

Participants

8

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 710903894-chloro-1,6-dimethyl-3-(3-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 71090315N-(1,6-dimethyl-3-(3-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methyl-1H-pyrazole-3-sulfonamideYield 20.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with 1-methyl-1H-pyrazole-3-sulfonamide (D94) (134 mg, 0.829 mmol), palladium(II) acetate (9.30 mg, 0.041 mmol), xantphos (47.9 mg, 0.083 mmol) and cesium carbonate (270 mg, 0.829 mmol). To this was added 4-chloro-1,6-dimethyl-3-(3-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine (D14) (135 mg, 0.414 mmol) dissolved in 1,4-dioxane (2.5 mL). The reaction mixture was heated at 150° C. in the microwave for 30 mins. The crude was purified on normal phase chromatography eluting with ethyl acetate in cyclohexane (0-80%) twice to give an impure material. The material was then dissolved in MeOH and passed through a SCX cartridge eluting with MeOH followed by 2M ammonia in MeOH to give a solid which was triturated with diethyl ether to give the title compound (38.7 mg). LCMS (A): m/z (M+H)+ 451, C23H26N6O2S requires 450 (acidic).

Workup

  1. customThe crude was purified on normal phase chromatography
  2. washeluting with ethyl acetate in cyclohexane (0-80%) twice
  3. customto give an impure material
  4. washeluting with MeOH
  5. customto give a solid which
  6. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-bbc3fd03a6de4e39a3e7c2a46e203920
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

Loading…