2-(Trimethylsilyl)ethanol → Tert-butyl 4-(1-(3,4-dichlorophenyl)-6-oxo-3-((2-(trimethylsilyl)ethoxy)carbonylamino)-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

HRID 386557Notes

Reaction equation

HRID 386557 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:16](C(O)=O)=[N:17][N:18]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=3)[C:19](=[O:21])[CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].P([N:49]=[N+]=[N-])(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1.[CH3:52][Si:53]([CH3:58])([CH3:57])[CH2:54][CH2:55][OH:56].[O:59]1[CH2:64]COCC1>>[Cl:29][C:24]1[CH:23]=[C:22]([N:18]2[C:19](=[O:21])[CH:20]=[C:15]([O:14][CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]3)[C:16]([NH:49][C:64]([O:56][CH2:55][CH2:54][Si:53]([CH3:58])([CH3:57])[CH3:52])=[O:59])=[N:17]2)[CH:27]=[CH:26][C:25]=1[Cl:28]

Participants

5

Reactant 4

HCID 180132-(Trimethylsilyl)ethanolHCID 312751,4-DioxaneHCID 123414Diphenylphosphoryl azideHCID 670726944-(1-(Tert-butoxycarbonyl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carboxylic acid

Product 1

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

Procedure

To a stirring solution of 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carboxylic acid (from example 15 step A) (48 mg, 0.10 mmol) in dioxane (10 mL) at room temperature under argon was added diphenyl phosphorazidate (65 mg, 0.20 mmol) and TEA (51 mg, 0.50 mmol). The resulting reaction mixture was stirred at room temperature for 1 hour, then 2-(trimethylsilyl)ethanol (118 mg, 1.0 mmol) was added. The resulting reaction mixture was heated at 80° C. under argon overnight. Solvent was concentrated. Crude reaction mixture was used directly to next step. MS (ESI) 597 (M−H).

Workup

  1. customThe resulting reaction mixture
  2. customThe resulting reaction mixture
  3. temperaturewas heated at 80° C. under argon overnight
  4. concentrationSolvent was concentrated
  5. customCrude reaction mixture

Sources & evidence

ORD record
ord-adaef01359534c8a8ab55598c1d4f7aa
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

Loading…