Hydrochloric Acid → N-(1-Benzyl-4,4-diethoxy-piperidin-3-yl)-6-(2-ethyl-5-fluoro-4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxamidine

HRID 340063Notes

Reaction equation

HRID 340063 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([O:17][CH2:18][CH3:19])([O:14][CH2:15][CH3:16])[CH:10]([NH:20][C:21]([C:23]2[C:31]3[C:26](=[CH:27][C:28]([C:32]4[CH:37]=[C:36]([F:38])[C:35]([O:39]COCC[Si](C)(C)C)=[CH:34][C:33]=4[CH2:48][CH3:49])=[CH:29][CH:30]=3)[N:25]([CH:50]3[CH2:55][CH2:54][CH2:53][CH2:52][O:51]3)[N:24]=2)=[NH:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(=O)([O-])O.[Na+]>C(O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([O:17][CH2:18][CH3:19])([O:14][CH2:15][CH3:16])[CH:10]([NH:20][C:21]([C:23]2[C:31]3[C:26](=[CH:27][C:28]([C:32]4[CH:37]=[C:36]([F:38])[C:35]([OH:39])=[CH:34][C:33]=4[CH2:48][CH3:49])=[CH:29][CH:30]=3)[N:25]([CH:50]3[CH2:55][CH2:54][CH2:53][CH2:52][O:51]3)[N:24]=2)=[NH:22])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 178467533N-(1-Benzyl-4,4-diethoxy-piperidin-3-yl)-6-[2-ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxamidine

Product 1

HCID 178467532N-(1-Benzyl-4,4-diethoxy-piperidin-3-yl)-6-(2-ethyl-5-fluoro-4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxamidineYield 100.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of N-(1-benzyl-4,4-diethoxy-piperidin-3-yl)-6-[2-ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxamidine (Preparation 8, 7.28 g, 9.4 mmol) in ethanol (32 mL) was added concentrated hydrochloric acid (12M, 3.92 mL, 47 mmol) and the resulting solution was allowed to stir at room temperature for 18 hours. The reaction mixture was cooled to 0° C. and neutralised by dropwise addition of a saturated aqueous solution of sodium hydrogen carbonate (150 mL). The mixture was extracted with EtOAc (2×200 mL). The combined organic layers were washed with further saturated aqueous sodium hydrogen carbonate solution (100 mL), dried over MgSO4 and concentrated in vacuo to give the title compound as a foam (6.06 g).

Workup

  1. extractionThe mixture was extracted with EtOAc (2×200 mL)
  2. washThe combined organic layers were washed with further saturated aqueous sodium hydrogen carbonate solution (100 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c14e944f5cd141b984e8248ca4809866
Source dataset
uspto-grants-2014_11
Patent number
US08895544B2

Reaction notes

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