Acetonitrile → 4-(4-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 60107Notes

Reaction equation

HRID 60107 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH:45]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:43]=[N:42]2)[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].C(#N)C.C(=O)([O-])[O-].[K+].[K+]>O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[C:28]([O:32][C:33]([N:35]1[CH2:36][CH2:37][CH:38]([N:41]2[CH:45]=[C:44]([C:2]3[CH:3]=[C:4]4[C:10]([C:11](=[O:12])[C:13]5[C:18]([F:19])=[CH:17][CH:16]=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[C:14]=5[F:27])=[CH:9][NH:8][C:5]4=[N:6][CH:7]=3)[CH:43]=[N:42]2)[CH2:39][CH2:40]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 119845561-Propanesulfonamide, N-[3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-HCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

Product 1

HCID 532621584-(4-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl esterYield 67.4%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

In a 10 mL microwave vial, propane-1-sulfonic acid [3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide (9, 51.0 mg, 0.111 mmol) and 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (34, 84.2 mg, 0.223 mmol) are combined with 0.680 mL of acetonitrile and potassium carbonate (0.34 mL, 1.00 M in water). 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8.3 mg, 0.011 mmol) is added and the mixture is heated at 160° C. in the microwave for 5 minutes, then diluted with water and extracted with ethyl acetate. The organic layer is washed with water, brine, and dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (P-1001, 47 mg). MS (ESI) [M+H+]+=629.0.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer is washed with water, brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. customThe resulting material is purified by silica gel column chromatography
  7. washeluting with ethyl acetate and hexane
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-568e140c3bcb4299b0d51a63880a45ae
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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