Methanol → 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

HRID 411216Notes

Reaction equation

HRID 411216 reaction equation
I[C:2]1[S:14][C:5]2[N:6]([CH3:13])[S:7](=[O:12])(=[O:11])[CH2:8][C:9](=[O:10])[C:4]=2[CH:3]=1.[CH2:15]([O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[C:16]#[CH:17].CO>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH3:13][N:6]1[C:5]2[S:14][C:2]([C:17]#[C:16][CH2:15][O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)=[CH:3][C:4]=2[C:9](=[O:10])[CH2:8][S:7]1(=[O:12])=[O:11]

Participants

6

Reactant 3

HCID 887MethanolHCID 98609Tetrahydro-2-(2-propynyloxy)-2H-pyranHCID 223971566-iodo-1-methyl-1H-thieno[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

Product 1

HCID 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-dioxideYield 66%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 1140TolueneSolvent

Procedure

To a stirring mixture of 6-iodo-1-methyl-1H-thieno[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide (Preparation 34, 1.0 g), triethylamine (1.5 mL) CuI (13.8 mg), and tetrahydro -2-(2-propynyloxy)-2H-pyran (0.49g) in toluene (50 mL) at ambient temperature is added tetrakis triphenylphosphine palladium (40 mg). The resulting mixture is stirred overnight at ambient temperature. MeOH (50 mL) is added, the mixture is stirred 20 min and the solvent is removed in vacuo. The residue is partitioned between 10% HCl/H2O/EtOAc (100 ml each), and the organic layer is separated. The solvent is removed in vacuo and the residue purified by flash column chromatography (4/1, hexanes/EtOAc) to afford 0.68 g (66%) of the title compound as a white solid. Physical characteristics: 1H NMR (CDCl3) δ 1.52-1.86, 3.39, 3.55, 3.84, 4.21, 4.45, 4.81, 7.38; MS (ESI−) m/z 354 (M−H)−. Anal. Found: C, 50.70; H, 4.89; N, 3.95.

Workup

  1. stirringthe mixture is stirred 20 min
  2. customthe solvent is removed in vacuo
  3. customThe residue is partitioned between 10% HCl/H2O/EtOAc (100 ml each)
  4. customthe organic layer is separated
  5. customThe solvent is removed in vacuo
  6. customthe residue purified by flash column chromatography (4/1, hexanes/EtOAc)

Sources & evidence

ORD record
ord-02f387b5b38642878b11420e9e9c991a
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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