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

HRID 1845903노트

반응식

HRID 1845903 반응식
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]

참가 물질

8

반응물 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

생성물 1

HCID 545788942-(1-{[2,2-Difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl)benzonitrile

시약·촉매·용매 3

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

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온도
100 °C

실험 절차

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.

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-2fbf791bc68b492d9f902075ed6218f1
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952005B2

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