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

HRID 515213

반응식

HRID 515213 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)촉매HCID 887Methanol용매HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-41a95e98bee941e2bb898733de405c0e
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108937B2

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