Cesium fluoride → (S)-2-((3-(3-fluoropyridin-2-yl)-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)oxy)-N-(1-(p-tolyl)ethyl)acetamide

HRID 402491ノート

反応式

HRID 402491 の反応式
Cl[C:2]1[C:10]2[C:5](=[N:6][C:7]([O:12][CH2:13][C:14]([NH:16][C@H:17]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)[CH3:18])=[O:15])=[CH:8][C:9]=2[CH3:11])[N:4]([CH3:26])[N:3]=1.[F-].[Cs+].[B-](F)(F)(F)F.CC([PH+](C(C)(C)C)C(C)(C)C)(C)C.[F:47][C:48]1[C:49]([Sn](CCCC)(CCCC)CCCC)=[N:50][CH:51]=[CH:52][CH:53]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.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].C(Cl)Cl>[F:47][C:48]1[C:49]([C:2]2[C:10]3[C:5](=[N:6][C:7]([O:12][CH2:13][C:14]([NH:16][C@H:17]([C:19]4[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=4)[CH3:18])=[O:15])=[CH:8][C:9]=3[CH3:11])[N:4]([CH3:26])[N:3]=2)=[N:50][CH:51]=[CH:52][CH:53]=1

参加物

9

反応物 5

HCID 25953Cesium fluorideHCID 516892Sodium BicarbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 164271503-Fluoro-2-(tributylstannyl)pyridineHCID 67209749(S)-2-((3-chloro-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)oxy)-N-(1-(p-tolyl)ethyl)acetamide

生成物 1

HCID 70817062(S)-2-((3-(3-fluoropyridin-2-yl)-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)oxy)-N-(1-(p-tolyl)ethyl)acetamide収率 6.6%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a sealed tube were added (S)-2-((3-chloro-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)oxy)-N-(1-(p-tolyl)ethyl)acetamide (50 mg, 0.13 mmol), Pd[P(tBu)3)]2 (3.4 mg, 6.7 μmol), CsF (45 mg, 0.30 mmol), [(t-Bu)3PH]BF4 (3.9 mg, 0.013 mmol) and Pd2(dba)3 (6.1 mg, 6.7 μmol). The tube was evacuated and flushed 3 times with argon and then 3-fluoro-2-tributylstannyl-pyridine (104 mg, 0.27 mmol) in dioxane (1 ml) was added and the suspension heated at 100° C. for 16 h. After cooling to rt, CH2Cl2 and NaHCO3 solution were added and the phases separated. The organic layers were washed with water, dried over Na2SO4 and the solvents removed under reduced pressure. Purification using preparative reverse phase chromatography (LC SunFire C18 OBD column) followed by liberation of the free base (SPE cartridge SCX-1, eluent 7M NH3 in methanol) yielded the title compound (3.7 mg, 6%). [1H-NMR (DMSO-d6, 600 MHz) δ 8.59 (d, 1H), 8.54 (d, 1H), 7.91 (t, 1H), 7.62-7.58 (m, 1H), 7.18 (d, 2H), 7.08 (d, 2H), 6.64 (s, 1H), 4.96 (q, 1H), 4.87 (d, 1H), 4.84 (d, 1H), 3.89 (s, 3H), 2.30 (s, 3H), 2.25 (s, 3H), 1.37 (d, 3H); HPLC-MS RtJ=1.08 min; [M+H]+=434.1]

後処理

  1. customThe tube was evacuated
  2. customflushed 3 times with argon
  3. temperatureAfter cooling to rt
  4. customthe phases separated
  5. washThe organic layers were washed with water
  6. dry with materialdried over Na2SO4
  7. customthe solvents removed under reduced pressure
  8. customPurification

出典と根拠

ORDレコード
ord-d5bcafd19315461abfb5697f3568c343
出典データセット
uspto-grants-2014_06
特許番号
US08742106B2

反応ノート

読み込み中…