Sodium Bicarbonate → 2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide

HRID 2234633Notes

Reaction equation

HRID 2234633 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH:10]=1.[NH2:37][C:38]1[C:48]([F:49])=[CH:47][C:46](I)=[CH:45][C:39]=1[C:40]([N:42]([CH3:44])[CH3:43])=[O:41].C(=O)(O)[O-].[Na+]>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].C(#N)C>[NH2:37][C:38]1[C:48]([F:49])=[CH:47][C:46]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[CH:10][N:11]([S:27]([C:30]4[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=4)(=[O:29])=[O:28])[C:12]3=[N:13][CH:14]=2)=[CH:45][C:39]=1[C:40]([N:42]([CH3:43])[CH3:44])=[O:41]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 160390673-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 577315392-amino-3-fluoro-5-iodo-N,N-dimethyl-benzamide

Product 1

HCID 577314782-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamideYield 81%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 6342AcetonitrileSolvent

Procedure

548 mg (1.09 mmol) of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine, 89 mg (0.109 mmol) of dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct and 368 mg (1.19 mmol) of 2-amino-3-fluoro-5-iodo-N,N-dimethyl-benzamide were placed in a microwave vial. To the vial were added 6 mL of acetonitrile and 5 mL of a saturated aqueous solution of sodium bicarbonate. The vial was sealed and purged with nitrogen and evacuated with vacuum (3×). The vial was irradiated in a microwave at 80° C. for 500 seconds. The resulting mixture was diluted with ethyl acetate and washed with water and brine. The layers were separated and the organic layer was dried over sodium sulfate and evaporated. The resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes. The clean fractions were concentrated to afford 490 mg (0.877 mmol, 81% yield) of 2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide as a peach foam. MS: m/z 559.2 (M+H+).

Workup

  1. customThe vial was sealed
  2. custompurged with nitrogen
  3. customevacuated with vacuum (3×)
  4. customThe vial was irradiated in a microwave at 80° C. for 500 seconds
  5. additionThe resulting mixture was diluted with ethyl acetate
  6. washwashed with water and brine
  7. customThe layers were separated
  8. dry with materialthe organic layer was dried over sodium sulfate
  9. customevaporated
  10. customThe resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes
  11. concentrationThe clean fractions were concentrated

Sources & evidence

ORD record
ord-d953d07c9a9a4cbe9401229cefa93e87
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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