Hydrazine → HCID 178461049, compound

HRID 2196694Notes

Reaction equation

HRID 2196694 reaction equation
C(OC([N:10]([CH3:12])C)N(C)C)(C)(C)C.[C:13]([C:16]1[C:24]2[C:19](=[N:20][CH:21]=[C:22]([NH:25][C:26](=[O:48])[C:27]3[C:32]([F:33])=[CH:31][CH:30]=[C:29]([N:34]([S:41]([CH2:44][CH2:45][CH3:46])(=[O:43])=[O:42])S(CCC)(=O)=O)[C:28]=3[F:47])[CH:23]=2)[N:18](S(CCC)(=O)=O)[CH:17]=1)(=O)[CH3:14].[NH2:55]N>C1COCC1>[NH:10]1[CH:12]=[CH:14][C:13]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[C:22]([NH:25][C:26](=[O:48])[C:27]4[C:32]([F:33])=[CH:31][CH:30]=[C:29]([NH:34][S:41]([CH2:44][CH2:45][CH3:46])(=[O:42])=[O:43])[C:28]=4[F:47])[CH:23]=3)[NH:18][CH:17]=2)=[N:55]1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 79885tert-Butoxy bis(dimethylamino)methaneHCID 131730124N-(3-acetyl-1-(propylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzamide

Product 1

HCID 178461049HCID 178461049, compoundYield 14.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-tert-butoxy-N,N,N′,N′-tetramethylmethanediamine (0.0132 mL, 0.0607 mmol) was added to N-(3-acetyl-1-(propylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzamide (0.0197 g, 0.0304 mmol) in THF (0.3 mL). The solution was stirred at reflux for 4 hours, cooled to room temperature and concentrated under reduced pressure. The resulting residue was taken up in EtOH (0.3 mL), and hydrazine (0.00973 g, 0.304 mmol) was added. The solution was stirred at reflux for 8 hours. The solution was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by column chromatography (5% to 10% MeOH/DCM), then purified again with reversed phase (C-18) chromatography using gradient elution with 1% to 50% CH3CN/water to afford N-(3-(1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (0.002 g, 0.0043 mmol, 14.3% yield). 1H NMR (400 MHz, CD3OD) δ 8.71-8.75 (m, 1H), 8.49-8.51 (m, 1H), 7.78 (s, 1H), 7.66-7.70 (m, 1H), 7.50-7.58 (m, 1H), 6.93-6.99 (m, 1H), 6.12-6.14 (m, 1H), 2.96-3.02 (m, 2H), 1.80-1.89 (m, 2H), 1.00-1.05 (m, 3H); m/z (APCI-pos) M+1=461.1.

Workup

  1. temperatureat reflux for 4 hours
  2. concentrationconcentrated under reduced pressure
  3. stirringThe solution was stirred
  4. temperatureat reflux for 8 hours
  5. temperatureThe solution was then cooled to room temperature
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by column chromatography (5% to 10% MeOH/DCM)
  8. custompurified again with reversed phase (C-18) chromatography
  9. washelution with 1% to 50% CH3CN/water

Sources & evidence

ORD record
ord-0fa6c87d50ed4e9c8fea2c209989e33e
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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