Potassium Fluoride → Mk-8033

HRID 1514632노트

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HRID 1514632 반응식
Cl[C:2]1[CH:3]=[C:4]2[C:12](=[O:13])[C:11]3[CH:14]=[C:15]([CH2:18][S:19]([NH:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)(=[O:21])=[O:20])[CH:16]=[CH:17][C:10]=3[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.[F-].[K+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH3:30][N:31]1[CH:35]=[C:34]([C:2]2[CH:3]=[C:4]3[C:12](=[O:13])[C:11]4[CH:14]=[C:15]([CH2:18][S:19]([NH:22][CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=5)(=[O:21])=[O:20])[CH:16]=[CH:17][C:10]=4[CH:9]=[CH:8][C:5]3=[N:6][CH:7]=2)[CH:33]=[N:32]1

참가 물질

7

반응물 4

HCID 522689Potassium FluorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57541262HCID 57541262, 화합물

생성물 1

HCID 45142457Mk-8033

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6228Dimethylformamide용매

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온도
130 °C

실험 절차

1-(3-Chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(pyridin-2-ylmethyl)methanesulfonamide (31.0 g, 72.8 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H pyrazole (22.72 g, 109 mmol), potassium fluoride (13.96 g, 240 mmol), tri-t-butylphosphonium tetrafluoroborate (2.112 g, 7.28 mmol), and Pd2(dba)3 (3.33 g, 3.64 mmol) were placed in a flask under an atmosphere of argon. DMF (364 ml) was added and argon was bubbled through the solution for several minutes. The solution was then heated at 130° C. for 6 h. The mixture was then cooled to room temperature, aqueous sodium hydrogen carbonate (saturated, 2000 mL) was added and the mixture was extracted with ethyl acatate (10×500 mL). The combined organic fractions were dried (anhydrous Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA to afford the title compound as a pale yellow solid. 1H NMR (600 MHz, DMSO-D6) δ 9.21 (d, 1H); 8.53 (d, 1H); 8.47 (m, 1H); 8.46 (m, 1H); 8.15 (d, 1H); 8.14 (s, 1H); 7.78 (m, 4H); 7.39 (m, 2H); 7.32 (d, 1H); 7.24 (m, 1H); 4.63 (s, 2H); 4.22 (d, 1H); 3.88 (s, 3H). LRMS (APCI) calculated for C25H21N5O3S [M+H]+, 472.1. found 472.1.

후처리

  1. customargon was bubbled through the solution for several minutes
  2. temperatureThe mixture was then cooled to room temperature
  3. additionaqueous sodium hydrogen carbonate (saturated, 2000 mL) was added
  4. extractionthe mixture was extracted with ethyl acatate (10×500 mL)
  5. dry with materialThe combined organic fractions were dried (anhydrous Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC Reverse phase (C-18)
  9. washeluting with Acetonitrile/Water+0.05% TFA

출처 및 근거

ORD 기록
ord-be55d2afd8ac41f888f78dab0a7aff91
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08222269B2

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