Acetic Acid → 2,2-Dimethyl-1-(5-(1-(4-(methylthio)benzyl)piperidin-3-ylamino)-1H-indazol-1-yl)propan-1-one

HRID 1911995Notes

Reaction equation

HRID 1911995 reaction equation
[CH3:1][C:2]([CH3:22])([CH3:21])[C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][CH:15]3[CH2:20][CH2:19][CH2:18][NH:17][CH2:16]3)=[CH:11][CH:12]=2)[CH:7]=[N:6]1)=[O:4].[CH3:23][S:24][C:25]1[CH:32]=[CH:31][C:28]([CH:29]=O)=[CH:27][CH:26]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:1][C:2]([CH3:22])([CH3:21])[C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][CH:15]3[CH2:20][CH2:19][CH2:18][N:17]([CH2:29][C:28]4[CH:31]=[CH:32][C:25]([S:24][CH3:23])=[CH:26][CH:27]=4)[CH2:16]3)=[CH:11][CH:12]=2)[CH:7]=[N:6]1)=[O:4]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 769854-(Methylthio)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 597997682,2-Dimethyl-1-(5-(piperidin-3-ylamino)-1H-indazol-1-yl)propan-1-one

Product 1

HCID 597997752,2-Dimethyl-1-(5-(1-(4-(methylthio)benzyl)piperidin-3-ylamino)-1H-indazol-1-yl)propan-1-oneYield 71.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Into a 25 mL round bottom flask were combined 2,2-dimethyl-1-(5-(piperidin-3-ylamino)-1H-indazol-1-yl)propan-1-one (0.250 g, 0.8 mmol), 1,2-dichloroethane (5 mL), 4-(methylthio)benzaldehyde (0.127 g, 0.8 mmol), glacial acetic acid (50 μL, 0.8 mmol), and sodium triacetoxyborohydride (0.229 g, 1.1 mmol). The reaction was evacuated and refilled with nitrogen. The reaction was monitored by HPLC and was complete upon the disappearance of the starting amine. The reaction was diluted with saturated sodium bicarbonate (10 mL) and dichloromethane (5 mL). After mixing, the organic phase was isolated, dried over MgSO4, filtered and concentrated to give the crude product. Chromatography of the residue on silica gel gave the title compound as an off-white solid (250 mg, 69%).

Workup

  1. customInto a 25 mL round bottom flask were combined
  2. customThe reaction was evacuated
  3. additionrefilled with nitrogen
  4. additionThe reaction was diluted with saturated sodium bicarbonate (10 mL) and dichloromethane (5 mL)
  5. additionAfter mixing
  6. customthe organic phase was isolated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product

Sources & evidence

ORD record
ord-a3af9ff584db48b092b1fd21d5c8b5e2
Source dataset
uspto-grants-2013_12
Patent number
US08604218B2

Reaction notes

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