Ethanol → 4-(2-(3-Oxa-8-azabicyclo[3.2.1]octan-8-yl)-4-(4-chlorophenyl)thiazol-5-yl)benzenesulfonamide

HRID 1051889Notes

Reaction equation

HRID 1051889 reaction equation
Br[C:2]1[S:6][C:5]([N:7]2[CH:12]3[CH2:13][CH2:14][CH:8]2[CH2:9][O:10][CH2:11]3)=[N:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1.C(O)C.[NH2:25][S:26]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)(=[O:28])=[O:27].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:12]12[N:7]([C:5]3[S:6][C:2]([C:32]4[CH:33]=[CH:34][C:29]([S:26]([NH2:25])(=[O:28])=[O:27])=[CH:30][CH:31]=4)=[C:3]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=4)[N:4]=3)[CH:8]([CH2:14][CH2:13]1)[CH2:9][O:10][CH2:11]2

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 223919774-(Aminosulphonyl)benzeneboronic acidHCID 898133608-(5-Bromo-4-(4-chlorophenyl)thiazol-2-yl)-3-oxa-8-azabicyclo[3.2.1]octane2×

Product 1

HCID 717368424-(2-(3-Oxa-8-azabicyclo[3.2.1]octan-8-yl)-4-(4-chlorophenyl)thiazol-5-yl)benzenesulfonamideYield 42%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
92.5 °C

Procedure

To a solution of 8-(5-bromo-4-(4-chlorophenyl)thiazol-2-yl)-3-oxa-8-azabicyclo[3.2.1]octane (Step 3 of compound 56, 0.26 g, 0.67 mmol) in a mixture of toluene:ethanol (2.5 ml:7.5 ml) were added 4-aminosulfonylbenzene boronic acid (0.15 g, 0.74 mmol) and potassium carbonate (0.23 g, 1.68 mmol) at 25° C. in a tube, the nitrogen gas was bubbled through reaction mixture for 15 minutes. To the reaction mixture was added tetrakis(triphenylphosphine)palladium(0) (0.039 g. 0.034 mmol) under nitrogen and the tube was sealed. The reaction mixture was heated at 90-95° C. for 18 hr with stirring. The progress of reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and filtered through celite. The residue was washed with mixture of 10% methanol in dichloromethane (2×20 ml). The filtrate was concentrated under reduced pressure to obtain a crude product; which was purified by flash column chromatography using 2-3% methanol in DCM as an eluent to obtain the title compound (0.13 g, 41.7%). MS: m/z 462 (M+1).

Workup

  1. customthe nitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customthe tube was sealed
  3. customThe progress of reaction
  4. temperatureThe reaction mixture was cooled to 25° C.
  5. filtrationfiltered through celite
  6. washThe residue was washed with mixture of 10% methanol in dichloromethane (2×20 ml)
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto obtain a crude product
  9. customwhich was purified by flash column chromatography

Sources & evidence

ORD record
ord-139a3d4b0ff24ead9a9859f2ead5eb01
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

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