Nitrogen → Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate

HRID 1854727노트

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HRID 1854727 반응식
Br[C:2]1[CH:3]=[C:4]2[C:11]([C:12]([NH:14][CH3:15])=[O:13])=[C:10]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[O:9][C:5]2=[N:6][C:7]=1[Cl:8].[C:23]([O:27][C:28]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+].N#N>O.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:7]1[N:6]=[C:5]2[O:9][C:10]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[C:11]([C:12](=[O:13])[NH:14][CH3:15])[C:4]2=[CH:3][C:2]=1[C:34]1[CH:35]=[C:30]([CH:31]=[CH:32][CH:33]=1)[C:28]([O:27][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:29]

참가 물질

8

반응물 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 2773299(3-((Tert-butoxy)carbonyl)phenyl)boronic acidHCID 904024175-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide

생성물 1

HCID 90402329Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate수율 88.7%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
65 °C

실험 절차

A mixture of 5-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide (5.0 g, 13 mmol), (3-(tert-butoxycarbonyl)phenyl)boronic acid (2.75 g, 12.4 mmol). Pd(Ph3P)4 (2.26 g, 1.96 mmol) and cesium carbonate (8.49 g, 26.1 mmol) was degassed/charged with N2 and diluted with water (22 ml)/DMF (220 ml). The resultant mixture was then degassed, charged with N2, heated to an internal temperature of 65° C. and allowed to stir under N2 atmosphere for 16 h. The reaction mixture was cooled to rt then diluted with EtOAc and sat. 1M HCl. The layers were separated and the aq layer was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with water, brine, dried over Na2SO4 filtered and concentrated. The resultant solid was then flashed on SiO2 eluting with a 0-100% EtOAc in hexanes gradient over 16 CV to give tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (5.2 g, 11 mmol, 83% yield) as a slightly yellow solid contaminated with the bis-coupled product di-tert-butyl 3,3′-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridine-5,6-diyl)dibenzoate. 1H NMR (500 MHz, CHLOROFORM-d) δ 8.18 (s, 1H), 8.08-8.02 (m, 2H), 7.95-7.89 (m, 2H), 7.63 (dt, J=7.6, 1.5 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 7.24-7.18 (m, 2H), 6.03 (d, J=4.3 Hz, 1H), 2.99 (d, J=4.9 Hz, 3H), 1.62 (s, 9H).

후처리

  1. customThe resultant mixture was then degassed
  2. additioncharged with N2
  3. temperatureThe reaction mixture was cooled to rt
  4. additionthen diluted with EtOAc and sat. 1M HCl
  5. customThe layers were separated
  6. extractionthe aq layer was extracted with EtOAc (3×10 mL)
  7. washThe combined organic extracts were washed with water, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

출처 및 근거

ORD 기록
ord-b2c3ea186613495bbbc3c36bf362270f
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962651B2

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