Cesium carbonate → 2-[1-(Cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-6-fluorobenzonitrile

HRID 515214Notes

Reaction equation

HRID 515214 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12](B4OC(C)(C)C(C)(C)O4)=[CH:13][C:8]=3[N:7]([CH3:23])[S:6]2(=[O:25])=[O:24])[CH2:3][CH2:2]1.Br[C:27]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[C:28]=1[C:29]#[N:30].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:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:27]4[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[C:28]=4[C:29]#[N:30])=[CH:13][C:8]=3[N:7]([CH3:23])[S:6]2(=[O:24])=[O:25])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27831392-Bromo-6-fluorobenzonitrileHCID 674228661-(Cyclopropylmethyl)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

Product 1

HCID 533802372-[1-(Cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-6-fluorobenzonitrile

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 1-(cyclopropylmethyl)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (2-1) (0.043 g, 0.12 mmol), 2-bromo-6-fluorobenzonitrile (0.035 g, 0.18 mmol), cesium carbonate (0.077 g, 0.24 mmol), palladium bis(tri-tert-butylphosphine) (0.012 g, 0.024 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]-6-fluorobenzonitrile (2-2) as a white solid. HRMS (M+H)+: observed=358.1015, calculated=358.1020

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-b9ea5e157821412aa2139a9acc37b357
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

Loading…