HCID 18416156, compound → HCID 18416152, compound

HRID 990965Notes

Reaction equation

HRID 990965 reaction equation
CC(C)([O-])C.[Na+].Br[C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[S:18][CH2:19][CH2:20][NH2:21])[N:14]=[C:13]([O:22][CH:23]([CH3:25])[CH3:24])[CH:12]=[C:11]2[C:26]([F:29])([F:28])[F:27]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:23]([O:22][C:13]1[CH:12]=[C:11]([C:26]([F:29])([F:28])[F:27])[C:10]2[CH:9]=[C:8]3[NH:21][CH2:20][CH2:19][S:18][C:17]3=[CH:16][C:15]=2[N:14]=1)([CH3:25])[CH3:24]

Participants

5

Reactant 2

HCID 18416156HCID 18416156, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 18416152HCID 18416152, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

A 10 mL Schlenk flask was charged with palladium acetate (10.7 mg, 0.0476 mmol), R-BINAP (32.6 mg, 0.0524 mmol) and sodium t-butoxide (0.137 g, 1.43 mmol). The flask was placed under vacuum, then bled with nitrogen. This process was repeated twice. The solids were dissolved in 3 mL toluene, and a solution of 2-{[6-bromo-2-isopropoxy-4-(trifluoromethyl)-7-quinolinyl]sulfanyl}-1-ethanamine (0.390 g, 0.953 mmol) in 3.3 mL toluene was added. The flask was heated to 100° C. for 4 h, whereupon the reaction was quenched with sat'd NH4Cl (30 mL) and water (30 mL). The mixture was extracted with EtOAc (2×60 mL), and the combined organic layers washed with brine (30 mL), dried over MgSO4, filtered, and concentrated. Flash chromatography (4:1 hexanes:EtOAc) afforded 0.242 g (77%) of 2,3-dihydro-7-isopropoxy-9-(trifluoromethyl)-1H-[1,4]thiazino[3,2-g]quinoline, a yellow solid. Data for 2,3-dihydro-7-isopropoxy-9-(trifluoromethyl)-1H-[1,4]thiazino[3,2-g]quinoline: 1H NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 6.99 (s, 1H), 6.90 (broad s, 1H), 5.44 (hept, 1H, J=6.2), 4.35 (broad s, 1H), 3.64-3.70 (m, 2H), 3.11-3.16 (m, 2H), 1.37 (d, 6H, J=6.2).

Workup

  1. customwas quenched with sat'd NH4Cl (30 mL) and water (30 mL)
  2. extractionThe mixture was extracted with EtOAc (2×60 mL)
  3. washthe combined organic layers washed with brine (30 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-2ae36fc90b364b4789e237aab07d0d9f
Source dataset
uspto-grants-2002_10
Patent number
US06462038B1

Reaction notes

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