Diethyl cyanophosphonate → N-[cis-1-Benzyl-6-(2-hydroxyethyl)piperidin-3-yl]-1-isopropyl-1H-indazole-3-carboxamide

HRID 602449Notes

Reaction equation

HRID 602449 reaction equation
[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([OH:15])=O)=[N:5]1)([CH3:3])[CH3:2].[NH2:16][C@H:17]1[CH2:22][N:21]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:20]([CH2:30][CH2:31][OH:32])[CH2:19][CH2:18]1.C(N(CC)C(C)C)(C)C.C(P(=O)(OCC)OCC)#N>CN(C)C=O>[CH2:23]([N:21]1[C@H:20]([CH2:30][CH2:31][OH:32])[CH2:19][CH2:18][C@H:17]([NH:16][C:13]([C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=2)=[O:15])[CH2:22]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 76257Diethyl cyanophosphonateHCID 81531DiisopropylethylamineHCID 106796951-Isopropyl-1H-indazole-3-carboxylic acidHCID 672707992-[cis-5-Amino-1-benzylpiperidin-2-yl]ethanol

Product 1

HCID 67270878N-[cis-1-Benzyl-6-(2-hydroxyethyl)piperidin-3-yl]-1-isopropyl-1H-indazole-3-carboxamideYield 57.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-isopropyl-1H-indazole-3-carboxylic acid (235 mg, 1.15 mmol), 2-[cis-5-amino-1-benzylpiperidin-2-yl]ethanol (322 mg, 1.37 mmol, step 8 of Example 1), N,N-diisopropylethylamine (177 mg, 1.37 mmol) in N,N-dimethylformamide (3 mL) was added diethyl cyanophosphonate (223 mg, 1.37 mmol) at room temperature. After stirring at room temperature for 20 h, the mixture was concentrated under reduced pressure. The resulting residue was chromatographed on a column of silica gel eluting with dichloromethane/methanol/25% ammonium hydroxide (10:1:0.2) to give 276 mg (52%) of the title compound as a colorless oil.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customThe resulting residue was chromatographed on a column of silica gel eluting with dichloromethane/methanol/25% ammonium hydroxide (10:1:0.2)

Sources & evidence

ORD record
ord-628b0bf49a864731b536be12a7e9763a
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

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