Acetonitrile → HCID 53261783, compound

HRID 60100Notes

Reaction equation

HRID 60100 reaction equation
[CH3:1][N:2]=[C:3]=[O:4].[F:5][C:6]1[C:11]([C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[CH:24]=[C:25]5[C:29](=[CH:30][CH:31]=4)[NH:28][N:27]=[CH:26]5)[CH:21]=3)[NH:16][CH:15]=2)=[O:13])=[C:10]([F:32])[CH:9]=[CH:8][C:7]=1[NH:33][S:34]([C:37]1[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:38]=1[F:44])(=[O:36])=[O:35].C(=O)([O-])[O-].[K+].[K+].C(#N)C>O.C(OCC)(=O)C.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>[CH3:1][NH:2][C:3]([N:28]1[C:29]2[C:25](=[CH:24][C:23]([C:20]3[CH:21]=[C:22]4[C:14]([C:12](=[O:13])[C:11]5[C:10]([F:32])=[CH:9][CH:8]=[C:7]([NH:33][S:34]([C:37]6[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:38]=6[F:44])(=[O:36])=[O:35])[C:6]=5[F:5])=[CH:15][NH:16][C:17]4=[N:18][CH:19]=3)=[CH:31][CH:30]=2)[CH:26]=[N:27]1)=[O:4]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 12228Methyl IsocyanateHCID 53261782N-(2,4-difluoro-3-[5-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-2,5-difluoro-benzenesulfonamide

Product 1

HCID 53261783HCID 53261783, compoundYield 72.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

Into a reaction flask, methyl isocyanate (6.5 mg, 0.11 mmol) is combined with N-{2,4-difluoro-3-[5-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-2,5-difluoro-benzenesulfonamide (P-0002, 22 mg, 0.031 mmol), tetrakis(triphenylphosphine)palladium(0) (2.2 mg, 0.0019 mmol), potassium carbonate (1.0 mL, 1.0 M in water) and 3 mL of acetonitrile. The reaction is heated at 140° C. for 50 minutes in a microwave, then diluted with water and ethyl acetate. The organic layer is washed with saturated sodium bicarbonate, then brine and dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with methanol and dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (P-0003, 14 mg, 72%). MS (ESI) [M+H+]+=623.

Workup

  1. washThe organic layer is washed with saturated sodium bicarbonate
  2. dry with materialbrine and dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under vacuum
  5. customThe resulting material is purified by silica gel column chromatography
  6. washeluting with methanol and dichloromethane
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-97c1aaf35b4b4ee3bf5e23f12f05c727
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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