Cesium carbonate → 2-[1-(Cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile

HRID 515213

Reaction equation

HRID 515213 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]2[N:6]([CH2:12][CH:13]3[CH2:15][CH2:14]3)[S:7](=[O:11])(=[O:10])[N:8]([CH3:9])[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:26]2[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=2[C:28]#[N:29])O1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>CO.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[Pd].O>[CH:13]1([CH2:12][N:6]2[C:5]3[CH:16]=[CH:17][C:2]([C:26]4[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=4[C:28]#[N:29])=[CH:3][C:4]=3[N:8]([CH3:9])[S:7]2(=[O:11])=[O:10])[CH2:15][CH2:14]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 35702292-(2-Cyanophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 674107445-Bromo-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

Product 1

HCID 533802362-[1-(Cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile

Reagents, catalysts & solvents 3

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added 5-bromo-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (1-4) (0.074 g, 0.23 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.070 g, 0.30 mmol), cesium carbonate (0.15 g, 0.47 mmol), palladium bis(tri-tert-butylphosphine) (0.024 g, 0.047 mmol), dioxane (1 mL), and water (0.2 mL). The reaction mixture was then heated under microwave irradiation at 100° C. for 10 minutes. The crude reaction mixture was then allowed to cool to room temperature, diluted with methanol, then filtered and concentrated. Purification of crude reaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 10% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water) to give 2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile (1-5). 1H NMR (400 MHz, CD3 OD): δ 7.82 (d, J=7.8 Hz, 1 H); 7.72 (t, J=7.7 Hz, 1 H); 7.61 (d, J=7.9 Hz, 1 H); 7.51 (t, J=7.7 Hz, 1 H); 7.22 (d, J=8.2 Hz, 1 H); 7.15-7.07 (m, 2H); 3.70 (d, J=6.8 Hz, 2 H); 3.31 (s, 3 H); 1.39-1.30 (m, 1 H); 0.66 (d, J=7.7 Hz, 2 H); 0.49 (d, J=5.1 Hz, 2 H). HRMS (M+H)+: observed=340.1114, calculated=340.1114.

Workup

  1. customThe crude reaction mixture
  2. temperatureto cool to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of crude
  6. customreaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 10% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water)

Sources & evidence

ORD record
ord-41a95e98bee941e2bb898733de405c0e
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Linked notes

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