Toluene → N-(4-(2-(4-carbamoylphenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676305노트

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HRID 1676305 반응식
[C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].[F:13][C:14]1[CH:15]=[C:16]([N:31]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=2)[C:32]([C:34]2([C:37]([NH2:39])=[O:38])[CH2:36][CH2:35]2)=[O:33])[CH:17]=[CH:18][C:19]=1[O:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]2[CH:27]=[C:28](I)[S:29][C:22]=12.C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>O.CCO>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:28]2[S:29][C:22]3[C:23](=[N:24][CH:25]=[CH:26][C:21]=3[O:20][C:19]3[CH:18]=[CH:17][C:16]([N:31]([C:40]4[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=4)[C:32]([C:34]4([C:37]([NH2:39])=[O:38])[CH2:36][CH2:35]4)=[O:33])=[CH:15][C:14]=3[F:13])[CH:27]=2)=[CH:6][CH:5]=1)(=[O:3])[NH2:2]

참가 물질

7

반응물 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 27378114-Aminocarbonylphenylboronic acidHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

생성물 1

HCID 67347374N-(4-(2-(4-carbamoylphenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide수율 13%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

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온도
80 °C

실험 절차

A sealable vial, was charged with 4-carbamoylphenylboronic acid (0.0312 g, 0.189 mmol), N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 0.100 g, 0.0947 mmol), Cs2CO3 (0.0309 g, 0.0947 mmol), toluene (2 mL) and EtOH (1 mL). Under nitrogen Pd(PPh3)4 (0.00547 g, 0.00473 mmol) was added and the reaction heated to 80° C. for 18 hours. The mixture was then cooled to room temperature, diluted with water (20 mL), and extracted with ethyl acetate (30 mL) and MeOH (2 mL). The organics were dried over sodium sulfate, filtered and concentrated to get crude product. The crude product was purified by reverse phase C-18 column chromatography to get product (6.9 mg, 13%) as a white solid. LRMS (esi+) 585 m/z (M+1) detected. 1H NMR (d6-DMSO, 400 MHz) δ 8.48 (d, J=6 Hz, 1H), 7.96 (m, 5H), 7.87 (m, 1H), 7.57 (m, 2H), 7.37 (m, 2H), 7.07 (t, J=9.0 Hz, 2H), 6.65 (d, J=6 Hz, 1H), 1.64 (s, 4H).

후처리

  1. additionUnder nitrogen Pd(PPh3)4 (0.00547 g, 0.00473 mmol) was added
  2. temperatureThe mixture was then cooled to room temperature
  3. extractionextracted with ethyl acetate (30 mL) and MeOH (2 mL)
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto get crude product
  8. customThe crude product was purified by reverse phase C-18 column chromatography

출처 및 근거

ORD 기록
ord-711cb9e2670e4ac38c69a34e63ac1aa5
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003662B2

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