Acetonitrile → propane-1-sulfonic acid {3-[5-(6-chloro-pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

HRID 217620Notes

Reaction equation

HRID 217620 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.[Cl:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C(#N)C.C(=O)([O-])[O-].[K+].[K+]>C(O)(=O)C>[Cl:28][C:29]1[N:34]=[CH:33][C:32]([C:2]2[CH:3]=[C:4]3[C:10]([C:11]([C:13]4[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]=4[F:19])=[O:12])=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 38450342-Chloropyridine-5-boronic acidHCID 119845561-Propanesulfonamide, N-[3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-

Product 1

HCID 49779383propane-1-sulfonic acid {3-[5-(6-chloro-pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Propane-1-sulfonic acid [3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide (56, 10 mg, 0.022 mmol) was weighed into a 5 mL microwave vial and combined with 6-chloro-pyridine-3-boronic acid (72, 4.4 mg, 0.028 mmol), followed by the addition of 600 μL of acetonitrile and 500 μL of 1M potassium carbonate and a spatula tip (˜1 mg) of [1,1″-bis(diphenylphosphino)-ferrocene]dichloropalladium(II). The reaction mixture was irradiated in a microwave at 160° C. for 5 minutes. The solution was neutralized with 100 μL of acetic acid and all material was transferred to a 4 mL vial and the solvents were removed under vacuum. The crude material was dissolved in 400 μL of dimtheylsulfoxide and purified by reverse phase HPLC, eluting with 0.1% trifluoroacetic acid in water and 0.1% trifluoroacetic acid in acetonitrile, 20-100% acetonitrile over 16 minutes at 6 mL per minute. Appropriate fractions were combined and the solvent removed under reduced pressure to provide the desired compound. MS (ESI) [M+H+]+=491.1.

Workup

  1. customThe reaction mixture was irradiated in a microwave at 160° C. for 5 minutes
  2. customthe solvents were removed under vacuum
  3. dissolutionThe crude material was dissolved in 400 μL of dimtheylsulfoxide
  4. custompurified by reverse phase HPLC
  5. washeluting with 0.1% trifluoroacetic acid in water and 0.1% trifluoroacetic acid in acetonitrile
  6. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-38c2d9f78b234269b2b4af2c8a256e17
Source dataset
uspto-grants-2012_06
Patent number
US08198273B2

Reaction notes

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