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

HRID 2234635Notes

Reaction equation

HRID 2234635 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:46]([F:47])=[CH:45][C:44](I)=[CH:43][C:39]=1[C:40]([OH:42])=[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:46]([F:47])=[CH:45][C:44]([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:28])=[O:29])[C:12]3=[N:13][CH:14]=2)=[CH:43][C:39]=1[C:40]([OH:42])=[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 577314632-Amino-3-fluoro-5-iodobenzoic acid

Product 1

HCID 577314302-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acidYield 78.6%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 6342AcetonitrileSolvent

Procedure

163 mg (0.323 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, 13 mg (0.016 mmol) of dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct, and 100 mg (0.356 mmol) of 2-amino-3-fluoro-5-iodo-benzoic acid were placed in a microwave vial. To the vial were added 2 mL of acetonitrile and 2 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 90° C. for 300 seconds. The resulting mixture was diluted with ethyl acetate and washed with water. The aqueous layer was back extracted three times with ethyl acetate. The combined organic phases were 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 135 mg (0.254 mmol, 78% yield) of 2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid as a brown residue. MS: m/z 532.0 (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 90° C. for 300 seconds
  5. additionThe resulting mixture was diluted with ethyl acetate
  6. washwashed with water
  7. extractionThe aqueous layer was back extracted three times with ethyl acetate
  8. dry with materialThe combined organic phases were 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-a4b87cea1ffd4b2095b2c0217df80374
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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