Cesium carbonate → Ethyl 1-(5-(2-(3-ethylureido)-7-(4-methylpyridin-2-yl)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

HRID 712255ノート

反応式

HRID 712255 の反応式
Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.B1(B2OCC(C)(C)CO2)OCC(C)(C)CO1.C([O-])(=O)C.[K+].Cl[C:57]1[CH:62]=[C:61]([CH3:63])[CH:60]=[CH:59][N:58]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O>[CH2:15]([NH:14][C:12]([NH:11][C:8]1[S:9][C:10]2[C:2]([C:57]3[CH:62]=[C:61]([CH3:63])[CH:60]=[CH:59][N:58]=3)=[CH:3][C:4]([C:17]3[CH:22]=[N:21][C:20]([N:23]4[CH2:24][CH2:25][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:27][CH2:28]4)=[N:19][CH:18]=3)=[CH:5][C:6]=2[N:7]=1)=[O:13])[CH3:16]

参加物

7

反応物 5

HCID 10796Cesium carbonateHCID 772482-Chloro-4-methylpyridineHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate2 回

生成物 1

HCID 86663970Ethyl 1-(5-(2-(3-ethylureido)-7-(4-methylpyridin-2-yl)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate収率 3.1%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
80 °C

実験手順

To a solution of ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (Intermediate 4) (0.5 g, 0.91 mmol) in DMSO (5 mL) was added bis(neopentylglycolato)diboron (0.41 g, 1.82 mmol) and potassium acetate (0.18 g, 1.82 mmol). The reaction was degassed by purging N2 for 15 min followed by addition of dichloro(1,1-bis(diphenylphosphino)ferrocene)palladium (II) (0.07 g, 0.091 mmol) and again degassed for 10-15 min then heated up to 80° C. for 2 h. After completion of reaction (TLC as well as MS monitoring), the reaction was cooled to rt followed by addition of 2-chloro-4-methylpyridine (0.23 g, 1.37 mmol) and an aqueous solution of Cs2CO3 (0.45 g, 1.37 mmol, dissolved in minimum amount of water). The reaction was degassed by purging N2 for 15 min followed by addition of tetrakis (triphenylphosphine)palladium(0) (0.11 g, 0.091 mmol) and again degassed for 10-15 min then heated up to 80° C. for 16 h. After reaction completion, 100 mL of ice-cold water was added then extracted with EtOAc (3×150 mL) and the combined organic layer was washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 1.50% MeOH: DCM to obtain a beige solid, which was further purified through preperative-HPLC to obtain the desired product as an off-white solid (0.016 g, 3%).

後処理

  1. customThe reaction was degassed
  2. customby purging N2 for 15 min
  3. customagain degassed for 10-15 min
  4. customAfter completion of reaction (TLC as well as MS monitoring), the reaction
  5. temperaturewas cooled to rt
  6. customThe reaction was degassed
  7. customby purging N2 for 15 min
  8. customagain degassed for 10-15 min
  9. temperaturethen heated up to 80° C. for 16 h
  10. customAfter reaction completion, 100 mL of ice-cold water
  11. additionwas added
  12. extractionthen extracted with EtOAc (3×150 mL)
  13. washthe combined organic layer was washed with brine
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. customevaporated under reduced pressure
  17. customThe crude residue was purified over 100-200 M silica-gel
  18. customDCM to obtain a beige solid, which
  19. customwas further purified through preperative-HPLC

出典と根拠

ORDレコード
ord-ca21846c681144a09ed964ca23e1a224
出典データセット
uspto-grants-2015_11
特許番号
US09181234B2

反応ノート

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