Hydrochloric Acid → N-(4-Chlorobenzyl)4-hydroxy-1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazine-3-carboxamide 2,2-Dioxide

HRID 411233Notes

Reaction equation

HRID 411233 reaction equation
[CH3:1][N:2]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]#[C:13][CH2:14][O:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][O:17]3)=[CH:11][C:6]=2[C:5](=[O:22])[CH2:4][S:3]1(=[O:24])=[O:23].C(N(CC)CC)C.[Cl:32][C:33]1[CH:42]=[CH:41][C:36]([CH2:37][N:38]=[C:39]=[O:40])=[CH:35][CH:34]=1.Cl>CS(C)=O>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([CH2:37][NH:38][C:39]([C:4]2[S:3](=[O:23])(=[O:24])[N:2]([CH3:1])[C:7]3[CH:8]=[CH:9][C:10]([C:12]#[C:13][CH2:14][O:15][CH:16]4[CH2:21][CH2:20][CH2:19][CH2:18][O:17]4)=[CH:11][C:6]=3[C:5]=2[OH:22])=[O:40])=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 33723791-Chloro-4-(isocyanatomethyl)benzeneHCID 223971711-Methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazin-4(3H)-one 2,2-Dioxide

Product 1

HCID 69732527N-(4-Chlorobenzyl)4-hydroxy-1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazine-3-carboxamide 2,2-DioxideYield 28.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazin4(3H)-one 2,2-dioxide (Preparation 52, 1.00 g) and triethylamine (0.60 mL) in DMSO (25 mL) is added a solution of 4-chlorobenzylisocyanate (0.72 g) inDMSO (5 mL) at ambient temperature. After 4 h, 10% HCl (100 mL) is added to the reaction vessel and the aqueous layer is extracted with EtOAc (3×100 mL). The organic layers are combined, dried over MgSO4, filtered, and concentrated in vacuo to afford 0.42g (28%) of the title compound as a lime green solid. Physical characteristics: m.p. 148-149° C.; 1H NMR (300 MHz, CDCl3) δ 15.81, 8.22, 7.93, 7.71, 7.33, 7.16, 4.91, 4.60, 4.52, 3.91, 3.60, 3.48, 1.86, 1.62; IR (diffuse reflectance) 3373, 2940, 1616, 1574, 1543, 1493, 1390, 1327, 1297, 1279, 1253, 1116, 1097, 1077, 1037 cm−1; MS (FAB) m/z 517 (MH+); HRMS (EI) m/z 516.1140 (C25H25ClN2O6S). Anal. Found: C, 57.55; H, 4.95; N, 5.63.

Workup

  1. extractionthe aqueous layer is extracted with EtOAc (3×100 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-426a6584054e4b0ba64df4d47cc856ab
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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