Cesium carbonate → 2-(1-{[2,2-Difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl)benzonitrile

HRID 1845903ノート

反応式

HRID 1845903 の反応式
Cl[C:2]1[N:7]=[C:6]2[S:8][C:9](=[O:17])[N:10]([CH2:11][CH:12]3[CH2:14][C:13]3([F:16])[F:15])[C:5]2=[CH:4][CH:3]=1.[C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O)#[N:19].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>CO.[Pd].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.O>[F:15][C:13]1([F:16])[CH2:14][CH:12]1[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[C:18]#[N:19])=[CH:3][CH:4]=2)[S:8][C:9]1=[O:17]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27346102-Cyanophenylboronic acidHCID 866765045-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one

生成物 1

HCID 545788942-(1-{[2,2-Difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-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-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one (1-5) (0.025 g, 0.090 mmol), (2-cyanophenyl)boronic acid (0.020 g, 0.14 mmol), cesium carbonate (0.059 g, 0.18 mmol), bis(tri-tert-butylphosphine) palladium (0.009 g, 0.02 mmol), 1,4-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, 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) gave 2-(1-{[2,2-difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl)benzonitrile (1-6) as a brown solid. 1H NMR (400 MHz, CD3OD): δ 7.87-7.72 (m, 5H); 7.60-7.54 (m, 1H); 4.25-4.10 (m, 2H); 2.23-2.15 (m, 1H); 1.61-1.54 (m, 1H); 1.38 (m, 1H). HRMS (M+H)+: observed=344.0669, calculated=344.0664.

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-2fbf791bc68b492d9f902075ed6218f1
出典データセット
uspto-grants-2015_02
特許番号
US08952005B2

反応ノート

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