Acetonitrile → HCID 46913048, compound

HRID 1397836Notes

Reaction equation

HRID 1397836 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.[CH3:28][O:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][N:31]=1.C(#N)C.C(=O)([O-])[O-].[K+].[K+]>C(O)(=O)C>[F:27][C:14]1[C:13]([C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:33]4[CH:32]=[N:31][C:30]([O:29][CH3:28])=[N:35][CH:34]=4)[CH:3]=3)[NH:8][CH:9]=2)=[O:12])=[C:18]([F:19])[CH:17]=[CH:16][C:15]=1[NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 119845561-Propanesulfonamide, N-[3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-

Product 1

HCID 46913048HCID 46913048, compound

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 (9, 10 mg, 0.022 mmol) was weighed into a 5 mL microwave vial and combined with 2-methoxypyrimidine-5-boronic acid (10, 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 dimetheylsulfoxide 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 vacuum to provide the desired compound P-0001. MS(ESI)[M+H+]+=487.9.

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 dimetheylsulfoxide
  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 vacuum

Sources & evidence

ORD record
ord-f459f417189a4abb8ff11998e61b1b55
Source dataset
uspto-grants-2014_12
Patent number
US08901301B2

Reaction notes

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