Thiosulfate ion → tert-butyl 4-[4-(1-amino-1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

HRID 1404609Notes

Reaction equation

HRID 1404609 reaction equation
[NH:1]1[C:9]2[C:4](=[N:5][CH:6]=[C:7]([C:10]3[CH:11]=[N:12][N:13]([CH:15]4[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]4)[CH:14]=3)[CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[NH2:30]Cl.S([O-])([O-])(=O)=S.[Cl-].[NH4+]>CN(C=O)C.CCOCC>[NH2:30][N:1]1[C:9]2[C:4](=[N:5][CH:6]=[C:7]([C:10]3[CH:11]=[N:12][N:13]([CH:15]4[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]4)[CH:14]=3)[CH:8]=2)[CH:3]=[CH:2]1

Participants

8

Reactant 5

HCID 1084Thiosulfate ionHCID 24758Sodium hydrideHCID 25423MonochloramineHCID 25517Ammonium ChlorideHCID 58532272tert-butyl 4-[4-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

Product 1

HCID 58532283tert-butyl 4-[4-(1-amino-1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateYield 45%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 4-[4-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate: (0.73 g, 2.0 mmol) in 4.0 mL of DMF at −20° C. was added NaH (60% in oil, 96 mg, 2.4 mmol) in one portion. After 15 min, the mixture was stirred at room temperature for 30 min. A solution of NH2Cl in Et2O (prepared according to the procedure described in J. Org. Chem. 2004, 1371: ˜0.15 M, 16 ml) was added. The mixture was poured into a saturated solution of thiosulfate and ammonium chloride, and extracted with ethyl acetate. The organic layer was concentrated and the product was purified by column chromatography (EtOAc:MeOH=100:5). The entitled intermediate was isolated as a light brown solid (350 mg, 45% yield) (starting material (220 mg) was also recovered).

Workup

  1. addition2004, 1371: ˜0.15 M, 16 ml) was added
  2. extractionextracted with ethyl acetate
  3. concentrationThe organic layer was concentrated
  4. customthe product was purified by column chromatography (EtOAc:MeOH=100:5)

Sources & evidence

ORD record
ord-3463d54ec13b48009f886ee808bba4e6
Source dataset
uspto-grants-2014_12
Patent number
US08912330B2

Reaction notes

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