Cesium carbonate → HCID 71711626, compound

HRID 528551Notes

Reaction equation

HRID 528551 reaction equation
[S:1]1[C:5]([NH:6][S:7]([C:10]2[CH:11]=[CH:12][C:13]3[NH:18][CH2:17][CH2:16][O:15][C:14]=3[CH:19]=2)(=[O:9])=[O:8])=[N:4][CH:3]=[N:2]1.Br[C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]#[N:24].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.CCOC(C)=O.Cl.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.C1(C)C=CC=CC=1>[C:23]([C:22]1[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=1[N:18]1[CH2:17][CH2:16][O:15][C:14]2[CH:19]=[C:10]([S:7]([NH:6][C:5]3[S:1][N:2]=[CH:3][N:4]=3)(=[O:9])=[O:8])[CH:11]=[CH:12][C:13]1=2)#[N:24]

Participants

11

Reactant 4

HCID 10796Cesium carbonate2×HCID 162722-BromobenzonitrileHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89761787HCID 89761787, compound2×

Product 1

HCID 71711626HCID 71711626, compoundYield 20.7%

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 313Hydrochloric AcidSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A vial was charged with N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE Z, 36 mg, 0.121 mmol), 2-bromobenzonitrile (32.9 mg, 0.181 mmol, Sigma-Aldrich, St. Louis, Mo.), Xantphos (13.96 mg, 0.024 mmol), Pd2(dba)3 (11.05 mg, 0.012 mmol), cesium carbonate (118 mg, 0.362 mmol), and toluene (1207 n1). The vial was sealed and placed in a 100° C. heating bath for 20 min, then 1,4-dioxane (1 mL) and cesium carbonate (180 mg) were added. The vial was heated overnight at 120° C., then the mixture was diluted with THF, EtOAc, and 1N aq. HCl. The mixture was extracted with EtOAC (3×), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The product was purified by chromatography on silica gel (12 g column, 0 to 10% MeOH/DCM to give 4-(2-cyanophenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (9.98 mg, 0.025 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.43 (s, 1 H), 8.01-7.92 (m, 1 H), 7.80 (dt, J=1.6, 7.8 Hz, 1 H), 7.59 (d, J=7.6 Hz, 1 H), 7.50 (dt, J=1.0, 7.7 Hz, 1 H), 7.23-7.05 (m, 2 H), 6.47 (d, J=8.4 Hz, 1 H), 4.40-4.24 (m, 2 H), 3.83-3.73 (m, 2 H). m/z (ESI) 400.2 (M+H)+.

Workup

  1. customThe vial was sealed
  2. customplaced in a 100° C.
  3. temperatureheating bath for 20 min
  4. extractionThe mixture was extracted with EtOAC (3×)
  5. dry with materialthe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by chromatography on silica gel (12 g column, 0 to 10% MeOH/DCM

Sources & evidence

ORD record
ord-24b292824f0249b5943c7ce0666dbb77
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

Loading…