Potassium Phosphate, Tribasic → 5-(11-fluoro-5,6-dihydropyridazino[4',3':3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595712노트

반응식

HRID 595712 반응식
Cl[C:2]1[N:19]=[N:18][C:5]2[CH2:6][CH2:7][N:8]3[C:16]4[CH:15]=[CH:14][CH:13]=[C:12]([F:17])[C:11]=4[CH:10]=[C:9]3[C:4]=2[CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B(O)O)=[CH:36][C:30]=3[C:31]=2[C:32](=[O:35])[NH:33][CH3:34])=[CH:23][CH:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[F:17][C:12]1[C:11]2[CH:10]=[C:9]3[C:4]4[CH:3]=[C:2]([C:37]5[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]6[O:28][C:27]([C:24]7[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=7)=[C:31]([C:32]([NH:33][CH3:34])=[O:35])[C:30]=6[CH:36]=5)[N:19]=[N:18][C:5]=4[CH2:6][CH2:7][N:8]3[C:16]=2[CH:15]=[CH:14][CH:13]=1

참가 물질

5

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 90332474(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acidHCID 903335802-Chloro-11-fluoro-5,6-dihydropyridazino[4',3':3,4]pyrido[1,2-a]indole

생성물 1

HCID 903410165-(11-fluoro-5,6-dihydropyridazino[4',3':3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide수율 13.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

To a degassed solution of 2-chloro-11-fluoro-5,6-dihydropyridazino[4′,3′:3,4]pyrido[1,2-a]indole (100 mg, 0.37 mmol), (2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acid (169 mg, 0.4 mmol) and K3PO4 (155 mg, 0.73 mmol) in DMF (3 mL) was added Pd(dtbpf)Cl2 (5 mg) under N2. Then the mixture was stirred at 100° C. for 3 hours. The reaction mixture was cooled to RT and filtered. The filtrate was washed with H2O and dried over Na2SO4. After being concentrated, the residue was purified by prep-HPLC to give the product of 5-(11-fluoro-5,6-dihydropyridazino[4′,3′:3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (30 mg, yield: 13%). 1H-NMR (CDCl3, 400 MHz) δ 8.11 (d, J=9.0 Hz, 2H), 8.00 (dd, J=5.6, 8.8 Hz, 2H), 7.66 (s, 1H), 7.25 (s, 1H), 7.15˜7.23 (m, 4H), 6.81 (dd, J=7.6, 9.6 Hz, 1H), 6.17 (d, J=4.0 Hz, 1H), 4.47 (t, J=6.4 Hz, 2H), 3.67 (t, J=6.4 Hz, 2H), 3.21 (s, 3H), 3.00 (d, J=4.8 Hz, 3H), 2.97 (s, 3H). MS (M+H)+: 614.

후처리

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O
  4. dry with materialdried over Na2SO4
  5. concentrationAfter being concentrated
  6. customthe residue was purified by prep-HPLC

출처 및 근거

ORD 기록
ord-9c882cbd7e7849cdbe15e902909de49e
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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