Cesium carbonate → (E)-tert-butyl 3-(6-(but-2-en-2-yl)-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate

HRID 1854764노트

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HRID 1854764 반응식
Cl[C:2]1[N:7]=[C:6]2[O:8][C:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[C:10]([C:11](=[O:14])[NH:12][CH3:13])[C:5]2=[CH:4][C:3]=1[C:22]1[CH:23]=[C:24]([CH:32]=[CH:33][CH:34]=1)[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].[CH3:35]/[C:36](/[B-](F)(F)F)=[CH:37]\[CH3:38].[K+].C1(P(C2CCCCC2)C2C(C3C(OC)=CC=CC=3OC)=CC(S([O-])(=O)=O)=CC=2)CCCCC1.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>C(O[Pd]OC(=O)C)(=O)C>[CH3:35]/[C:36](/[C:2]1[N:7]=[C:6]2[O:8][C:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[C:10]([C:11](=[O:14])[NH:12][CH3:13])[C:5]2=[CH:4][C:3]=1[C:22]1[CH:23]=[C:24]([CH:32]=[CH:33][CH:34]=1)[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:37]\[CH3:38]

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 71310868Potassium (Z)-but-2-en-2-yltrifluoroborateHCID 90402329Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoateHCID 90402412Sodium 6-(dicyclohexylphosphino)-2',6'-dimethoxy-[1,1'-biphenyl]-3-sulfonate

생성물 1

HCID 90402428(E)-tert-butyl 3-(6-(but-2-en-2-yl)-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate수율 45.4%

시약·촉매·용매 1

HCID 167845palladium(II) acetate촉매

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온도
80 °C

실험 절차

tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (250 mg, 0.520 mmol), potassium (Z)-but-2-en-2-yltrifluoroborate (100 mg, 0.617 mmol), sodium 6-(dicyclohexylphosphino)-2′,6′-dimethoxy-[1,1′-biphenyl]-3-sulfonate (107 mg, 0.208 mmol), diacetoxypalladium (23.3 mg, 0.104 mmol), cesium carbonate (254 mg, 0.780 mmol) were combined dry, degassed with N2 and then taken up in DMF (4.7 ml) and water (0.47 ml) and heated to 80° C. for 1 h. The reaction was then concentrated to dryness azeotroping with toluene and the crude mixture was adsorbed onto Celite and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) give the expected product (E)-tert-butyl 3-(6-(but-2-en-2-yl)-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (118 mg, 0.236 mmol, 45% yield) consistent by LCMS and NMR. LC-MS retention time: 2.22 min; m/z (MH+): 501. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (400 MHz, DMSO-d6) δ 8.51-8.43 (m, 1H), 8.10-8.04 (m, 2H), 8.01 (s, 1H), 7.96-7.93 (m, 1H), 7.91-7.87 (m, 1H), 7.68-7.64 (m, 1H), 7.60-7.54 (m, 1H), 7.45-7.37 (m, 2H), 5.44-5.37 (m, 1H), 2.83 (d, J=4.5 Hz, 3H), 1.87-1.82 (m, 3H), 1.59-1.52 (m, 12H).

후처리

  1. customdegassed with N2
  2. concentrationThe reaction was then concentrated to dryness
  3. customazeotroping with toluene
  4. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

출처 및 근거

ORD 기록
ord-92f06adc6e654fd5b83e84c0a19d9ad6
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962651B2

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