Tetrabutylammonium Fluoride → Tert-butyl 4-(3-amino-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

HRID 386558Notes

Reaction equation

HRID 386558 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[C:11]([NH:30]C(OCC[Si](C)(C)C)=O)=[N:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:30][C:11]1[C:12]([O:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:13][C:14](=[O:15])[N:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[N:10]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67445040Tert-butyl 4-(1-(3,4-dichlorophenyl)-6-oxo-3-((2-(trimethylsilyl)ethoxy)carbonylamino)-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 44621662Tert-butyl 4-(3-amino-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylateYield 61.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of tert-butyl 4-(1-(3,4-dichlorophenyl)-6-oxo-3-((2-(trimethylsilyl)ethoxy)carbonylamino)-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (60 mg, 0.10 mmol) in THF (10 ml) at room temperature under argon was added 1M TBAF in THF (1 mL, 1.0 mmol). The reaction mixture was stirred at room temperature overnight. Solvent was removed in vacuo. The crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA) to give tert-butyl 4-(3-amino-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (28 mg, white solid, 55%). 1H NMR (400 MHz, CDCl3) δ ppm 1.34-1.55 (m, 9H) 1.65-1.91 (m, 2H) 2.04 (dd, J=12.96, 3.30 Hz, 2H) 3.06-3.39 (m, 2H) 3.59-3.94 (m, 2H) 4.29-4.71 (m, 2H) 6.20 (s, 1H) 7.43-7.50 (m, 1H) 7.54-7.64 (m, 1H) 7.80 (d, J=2.20 Hz, 1H). MS (ESI) 455 (M+H).

Workup

  1. customSolvent was removed in vacuo
  2. customThe crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA)

Sources & evidence

ORD record
ord-c4066add6c0845b69f824dfe12787438
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

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