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

HRID 515213

反応式

HRID 515213 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)触媒HCID 887Methanol溶媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-41a95e98bee941e2bb898733de405c0e
出典データセット
uspto-grants-2015_08
特許番号
US09108937B2

関連ノート

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