Sodium Dithionite → 2-Amino-N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-piperidin-1-ylmethyl benzamide

HRID 571923Notes

Reaction equation

HRID 571923 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[NH:15][C:16](=[O:33])[C:17]1[CH:22]=[CH:21][C:20]([CH2:23][N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:19][C:18]=1[N+:30]([O-])=O.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(Cl)Cl.[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].O>[NH2:30][C:18]1[CH:19]=[C:20]([CH2:23][N:24]2[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]2)[CH:21]=[CH:22][C:17]=1[C:16]([NH:15][C:9]1[C:8]2[C:12](=[CH:13][CH:14]=[C:6]([CH2:5][C:4]3[CH:34]=[C:35]([F:37])[CH:36]=[C:2]([F:1])[CH:3]=3)[CH:7]=2)[NH:11][N:10]=1)=[O:33]

Participants

6

Reactant 2

HCID 24489Sodium DithioniteHCID 68672122N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-2-nitro-4-piperidin-1-ylmethyl-benzamide

Product 1

HCID 686724042-Amino-N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-piperidin-1-ylmethyl benzamideYield 103.3%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-2-nitro-4-piperidin-1-ylmethyl-benzamide (255 mg, 0.505 mmol) was suspended in DCM (7 mL) and treated with nBu4NCl (95 mg, 0.343 mmol). Na2S2O4 (659 mg, 3.029 mmol) in water (3.4 mL) was added drop-wise, with stirring. After 2 hours, the volatiles were removed by evaporation, a solid was filtered from the aqueous phase and dried under vacuum. The solid was treated with 4N HCl in dioxane (12 mL) and the solvent was then removed by evaporation. The solid was dissolved in DCM (100 mL), washed with aqueous K2CO3 and then with brine. After drying over sodium sulphate and removal of the solvent, 248 mg of title compound were obtained in more than quantitative yield. The crude was employed in the following step with no further purification.

Workup

  1. customthe volatiles were removed by evaporation
  2. filtrationa solid was filtered from the aqueous phase
  3. customdried under vacuum
  4. additionThe solid was treated with 4N HCl in dioxane (12 mL)
  5. customthe solvent was then removed by evaporation
  6. dissolutionThe solid was dissolved in DCM (100 mL)
  7. washwashed with aqueous K2CO3
  8. dry with materialAfter drying over sodium sulphate and removal of the solvent

Sources & evidence

ORD record
ord-2b50415e09c14cc3a4156aaa26640fc9
Source dataset
uspto-grants-2015_05
Patent number
US09029356B2

Reaction notes

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