Potassium Carbonate → tert-Butyl (5-{[4-{[4-(difluoromethoxy)phenyl]amino}-1,1-dioxido-3-oxo-5-phenylisothiazol-2(3H)-yl]methyl}pyridin-2-yl)carbamate

HRID 729268Notes

Reaction equation

HRID 729268 reaction equation
[F:1][CH:2]([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][CH:5]=1.Cl[C:13]1[C:14](=[O:26])[NH:15][S:16](=[O:25])(=[O:24])[C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[C:27]([O:31][C:32](=[O:42])[NH:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40]Br)=[CH:36][N:35]=1)([CH3:30])([CH3:29])[CH3:28].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:1][CH:2]([F:11])[O:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:13]2[C:14](=[O:26])[N:15]([CH2:40][C:37]3[CH:38]=[CH:39][C:34]([NH:33][C:32](=[O:42])[O:31][C:27]([CH3:29])([CH3:28])[CH3:30])=[N:35][CH:36]=3)[S:16](=[O:25])(=[O:24])[C:17]=2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 7373634-(Difluoromethoxy)anilineHCID 23030321tert-Butyl (5-(bromomethyl)pyridin-2-yl)carbamateHCID 686616564-Chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 86623729tert-Butyl (5-{[4-{[4-(difluoromethoxy)phenyl]amino}-1,1-dioxido-3-oxo-5-phenylisothiazol-2(3H)-yl]methyl}pyridin-2-yl)carbamateYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[4-[Difluoromethoxy)phenyl]amine (0.27 g, 1.7 mmol) was added to an ice cold solution of 4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.41 g, 1.7 mmol) in DMF (4 ml) and the mixture was stirred for 1 h. tert-Butyl[5-(bromomethyl)pyridin-2-yl]carbamate (0.48 g, 1.7 mmol) and anhydrous potassium carbonate (0.23 g, 1.7 mmol) were added. The reaction mixture was stirred over night, concentrated and the residue was dissolved in DCM. The mixture was washed with water and concentrated and the residue was purified using preparative HPLC to give the title compound (0.12 g, 13%). 1H NMR (400 MHz, d6-DMSO): δ 1.41 (s, 9H), 3.77 (dd, 2H), 7.22-7.24 (m, 3H), 7.27 (t, 1H), 7.39-7.45 (m, 5H), 7.48 (d, 1H), 7.78 (d, 1H), 7.86 (dd, 2H), 9.57 (s, 1H), 11.18 (s, 1H); Mass Spectrum: M+H+ 573.

Workup

  1. additionwere added
  2. concentrationconcentrated
  3. dissolutionthe residue was dissolved in DCM
  4. washThe mixture was washed with water
  5. concentrationconcentrated
  6. customthe residue was purified

Sources & evidence

ORD record
ord-a0e16348babc42139ec1a602863c685a
Source dataset
uspto-grants-2009_09
Patent number
US07582629B2

Reaction notes

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