Cesium carbonate → 4-(6-Chloro-7-methoxy-2,3-dimethyl-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide

HRID 1618645Notes

Reaction equation

HRID 1618645 reaction equation
[N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[S:15](=[O:17])(=[O:16])[CH2:14][CH2:13][NH:12][C:11]=3[CH:18]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl[C:20]1[C:29]2[C:24](=[CH:25][C:26]([O:31][CH3:32])=[C:27]([Cl:30])[CH:28]=2)[N:23]=[C:22]([CH3:33])[C:21]=1[CH3:34].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.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]>[Cl:30][C:27]1[CH:28]=[C:29]2[C:24](=[CH:25][C:26]=1[O:31][CH3:32])[N:23]=[C:22]([CH3:33])[C:21]([CH3:34])=[C:20]2[N:12]1[C:11]2[CH:18]=[C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)[CH:8]=[CH:9][C:10]=2[S:15](=[O:17])(=[O:16])[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 672847356-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxideHCID 672854564,6-Dichloro-7-methoxy-2,3-dimethylquinoline

Product 1

HCID 672853524-(6-Chloro-7-methoxy-2,3-dimethyl-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide

Reagents, catalysts & solvents 2

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

Procedure

Prepared according to procedure T using 6-morpholin-4-yl-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide (0.134 g, 0.5 mmol), 4,6-dichloro-7-methoxy-2,3-dimethylquinoline (0.256 g, 1 mmol), cesium carbonate (0.326 g, 1 mmol), Pd2(dba)3 (0.046 g, 0.05 mmol) and (±) BINAP (0.047 g, 0.075 mmol) in 1,4-dioxane (2 mL). After purification by HPLC 4-(6-chloro-7-methoxy-2,3-dimethyl-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide was obtained. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.10 (1H, s), 7.60 (1H, s), 7.48-7.54 (1H, m), 6.56 (1H, m), 5.51 (1H, dd, J=1.8, 0.9 Hz), 4.12 (2H, br. s.), 3.93 (3H, s), 3.56 (4H, dd, J=5.1, 4.6 Hz), 2.87 (4H, dd, J=5.3, 4.8 Hz), 2.72 (3H, s), 2.55 (2H, m). Mass Spectrum (ESI) m/e=489 (M+1).

Workup

  1. customPrepared
  2. customAfter purification by HPLC 4-(6-chloro-7-methoxy-2,3-dimethyl-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzothiazine 1,1-dioxide
  3. customwas obtained

Sources & evidence

ORD record
ord-428c023ca7d5400ebf600ed9442bd5a5
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

Loading…