Morpholine → HCID 68182917, compound

HRID 1615583Notes

Reaction equation

HRID 1615583 reaction equation
Cl[C:2]1[S:10][C:9]2[S:8](=[O:12])(=[O:11])[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH2:6][C:5]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)([OH:21])[C:4]=2[CH:3]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:80]1[CH2:85][CH2:84][O:83][CH2:82][CH2:81]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[N:80]1([C:2]2[S:10][C:9]3[S:8](=[O:12])(=[O:11])[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH2:6][C:5]([C:22]4[CH:31]=[CH:30][C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH:23]=4)([OH:21])[C:4]=3[CH:3]=2)[CH2:85][CH2:84][O:83][CH2:82][CH2:81]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 68182961HCID 68182961, compound

Product 1

HCID 68182917HCID 68182917, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A 5 mL microwave vial was charged with 6-chloro-4-(2-naphthyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide (0.140 g, 0.282 mmol, tris(dibenzylideneacetone)dipalladium(0) (0.0129 g, 0.0141 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.0163 g, 0.0282 mmol) and cesium carbonate (0.2758 g, 0.8466 mmol). The vial was flushed with Ar and 1,4-dioxane (4.4 mL) and morpholine (0.0738 mL, 0.847 mmol) were added. The reaction mixture was sealed and heated at microwave irradiation to 140° C. for 1 hour. Solvent was evaporated, and the residue was purified using column chromatography on silica gel (24 g Analogix column, gradient hexane to 50% EA in hexane over 20 minutes) to provide the title compound (0.030 g, 18%). LCMS (FA) ES+: 547. 1H NMR (400 MHz, DMSO) δ 7.94-7.88 (m, 4H), 7.53-7.51 (m, 2H), 7.30-7.27 (m, 1H), 6.50 (s, 1H), 5.69 (s, 1H), 4.87 (d, 1H), 4.53 (d, 1H), 4.11 (d, 1H), 3.87 (d, 1H), 3.64-3.61 (m, 4H), 3.50-3.45 (m, 2H), 3.06-3.03 (m, 4H), 0.79-0.74 (m, 2H), −0.06 (s, 9H).

Workup

  1. additionwere added
  2. customThe reaction mixture was sealed
  3. customSolvent was evaporated
  4. customthe residue was purified
  5. customon silica gel (24 g Analogix column, gradient hexane to 50% EA in hexane over 20 minutes)

Sources & evidence

ORD record
ord-dd1a3c92f91d4721ac75330abc08bc53
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

Loading…