Triethylamine → N-(4-Chlorobenzyl)4-hydroxy-1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazine-3-carboxamide 2,2-Dioxide

HRID 411217Notes

Reaction equation

HRID 411217 reaction equation
[CH3:1][N:2]1[C:7]2[S:8][C:9]([C:11]#[C:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)=[CH:10][C:6]=2[C:5](=[O:21])[CH2:4][S:3]1(=[O:23])=[O:22].C(N(CC)CC)C.[Cl:31][C:32]1[CH:41]=[CH:40][C:35]([CH2:36][N:37]=[C:38]=[O:39])=[CH:34][CH:33]=1>CS(C)=O.Cl>[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:36][NH:37][C:38]([C:4]2[S:3](=[O:22])(=[O:23])[N:2]([CH3:1])[C:7]3[S:8][C:9]([C:11]#[C:12][CH2:13][O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][O:16]4)=[CH:10][C:6]=3[C:5]=2[OH:21])=[O:39])=[CH:40][CH:41]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 33723791-Chloro-4-(isocyanatomethyl)benzeneHCID 223972121-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

Product 1

HCID 69731037N-(4-Chlorobenzyl)4-hydroxy-1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazine-3-carboxamide 2,2-DioxideYield 31%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirring solution of 1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide (Preparation 35, 0.64 g) and triethylamine (0.27 g) in DMSO (15mL) at ambient temperature is added 4-chloro-benzylisocyanate (0.45 g). The resulting red solution is stirred overnight at ambient temperature and diluted with 10% aqueous HCl (20 mL). The aqueous layer is extracted with EtOAc (3×25 ml). The combined organic layers are dried over MgSO4 and concentrated in vacuo. The residue is dissolved in EtOAc (15 mL) and allowed to stand at ambient temperature overnight. The resulting solid is collected by filtration, washed with EtOAc (10 ml) and dried in vacuo at 50° C. to afford 0.29 g (31%) of the title compound as a tan solid. Physical characteristics: 1H NMR (CDCl3) δ 1.58-1.82, 3.49, 3.60, 3.89, 4.50, 4.56, 4.86, 7.30, 7.42, 7.71, 15.62; IR (diffuse reflectance) 3353, 2945, 1615, 1581, 1541, 1493, 1431, 1366, 1345, 1308, 1296, 1276, 1183, 1119, 1031 cm−1; MS (EI) m/z 522 (M+). Anal. Found: C, 53.17; H, 4.49; N, 5.67.

Workup

  1. extractionThe aqueous layer is extracted with EtOAc (3×25 ml)
  2. dry with materialThe combined organic layers are dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue is dissolved in EtOAc (15 mL)
  5. waitto stand at ambient temperature overnight
  6. filtrationThe resulting solid is collected by filtration
  7. washwashed with EtOAc (10 ml)
  8. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-9260289da59b44bd9b1bf1cf3cabe18b
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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