p-Toluenesulfonic acid monohydrate → N-(4-Chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-1-methyl-1H-2,1-benzothiazine-3-carboxamide 2,2-Dioxide

HRID 1070652Notes

Reaction equation

[Cl:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:11](=[O:33])(=[O:32])[N:12]([CH3:31])[C:13]3[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][O:24]C4CCCCO4)=[CH:17][C:14]=3[C:15]=2[OH:16])=[O:9])=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:11](=[O:33])(=[O:32])[N:12]([CH3:31])[C:13]3[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][OH:24])=[CH:17][C:14]=3[C:15]=2[OH:16])=[O:9])=[CH:34][CH:35]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 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 (Preparation 53, 0.30 g) in CH3OH (30 mL) is added p-TsOH.H2O (30 mg). The reaction mixture is heated to 55° C. for 2 h. The solvent is evaporated in vacuo and the residue is diluted with Et2O (20 mL) and sonicated. The resulting precipitate is filtered and washed with Et2O to afford 0.16 g (61%) of the title compound as a white solid. Physical characteristics: m.p. 167-168° C.; 1H NMR (300 MHz, CDCl3) δ15.82, 8.21, 7.93, 7.69, 7.36, 7.17, 4.60, 4.53, 3.49, 2.21; IR (diffuse reflectance) 3344, 1615, 1579, 1554, 1540, 1490, 1392, 1385, 1325, 1310, 1293, 1279, 1160, 1093, 1031 cm−1; MS (ESI+) m/z 433 (MH+); HRMS (FAB) m/z 433.0614 (C20H17ClN2O5S+H). Anal. Found: C, 54.57; H, 4.16; N, 6.10.

Workup

customThe solvent is evaporated in vacuo
additionthe residue is diluted with Et2O (20 mL)
customsonicated
filtrationThe resulting precipitate is filtered
washwashed with Et2O

Sources & evidence

ORD record: ord-9fd1e834b9f64dbbb32a0c3f99752b12
Source dataset: uspto-grants-2005_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06903097B2

Reaction notes

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