Trifluoroacetic acid → N-[6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide

HRID 520651Notes

Reaction equation

HRID 520651 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:18]=[C:17]([Sn](C)(C)C)[CH:16]=[C:15]3[C:11]=2[CH:12]=[N:13][N:14]3S(C2C=CC=CC=2)(=O)=O)=[O:8])[N:6]=1.[F:32][C:33]1[C:34](I)=[C:35]2[CH:41]=[CH:40][N:39](S(C3C=CC([N+]([O-])=O)=CC=3)(=O)=O)[C:36]2=[N:37][CH:38]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.CC#N>[F:32][C:33]1[C:34]([C:17]2[CH:16]=[C:15]3[C:11]([CH:12]=[N:13][NH:14]3)=[C:10]([NH:9][C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][CH:4]=3)=[O:8])[CH:18]=2)=[C:35]2[CH:41]=[CH:40][NH:39][C:36]2=[N:37][CH:38]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 582558202-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamideHCID 666919775-fluoro-4-iodo-1-[(4-nitrophenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 53233428N-[6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Procedure

2-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (1 g) was dissolved in DMF (4 ml) and 400 μl of the resultant solution was dispensed to 5-fluoro-4-iodo-1-[(4-nitrophenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine (0.18 mmol) in DMF (400 μl) in a microwave vessel. Solvias catalyst (4 mg) was added and the reaction was heated in the microwave using initial 700 W to 135° C. for 20 min. The solution was loaded onto C18 SPE (pre-conditioned with 0.1% TFA in MeCN) and flushed through with 0.1% TFA in MeCN (3 ml). The solvent was removed under nitrogen blowdown. The sample was dissolved in DMSO (0.5 ml) and purified by MDAP (method D). The solvent was evaporated in vacuo using the Genevac. The sample was dissolved in IPA (300 μl) and 2M NaOH (aq) (300 μl) was added. The reaction was left overnight. The sample was dissolved in DMSO (0.6 ml) and purified by MDAP (method M). The solvent was evaporated in vacuo using the Genevac to give title compound, 2 mg.

Workup

  1. temperaturethe reaction was heated in the microwave
  2. customfor 20 min
  3. customflushed through with 0.1% TFA in MeCN (3 ml)
  4. customThe solvent was removed under nitrogen
  5. dissolutionThe sample was dissolved in DMSO (0.5 ml)
  6. custompurified by MDAP (method D)
  7. customThe solvent was evaporated in vacuo
  8. dissolutionThe sample was dissolved in IPA (300 μl)
  9. addition2M NaOH (aq) (300 μl) was added
  10. dissolutionThe sample was dissolved in DMSO (0.6 ml)
  11. custompurified by MDAP (method M)
  12. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-4dce32194c6142329f8400766a33609a
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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