Potassium Phosphate, Tribasic → (3R,3aR,6R,6aR)-6-((6-chloro-5-(2-fluoro-[1,1'-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

HRID 929239ノート

反応式

HRID 929239 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[N:11](COCC[Si](C)(C)C)[C:10]([O:20][C@H:21]3[C@H:25]4[O:26][CH2:27][C@@H:28]([OH:29])[C@H:24]4[O:23][CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1I.[F:30][C:31]1[CH:36]=[C:35](B(O)O)[CH:34]=[CH:33][C:32]=1[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CS(C)=O.CC([P+](Cl)(C(C)(C)C)C(C)(C)C)(C)C.C1C=CC(C2C(N)=CC=CC=2)=CC=1.[Pd+2]>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([O:20][C@H:21]3[C@H:25]4[O:26][CH2:27][C@@H:28]([OH:29])[C@H:24]4[O:23][CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1[C:35]1[CH:34]=[CH:33][C:32]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)=[C:31]([F:30])[CH:36]=1

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 27746982-Fluoro-4-biphenylboronic AcidHCID 90042470(3R,3aR,6R,6aR)-6-((6-chloro-5-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

生成物 1

HCID 90067395(3R,3aR,6R,6aR)-6-((6-chloro-5-(2-fluoro-[1,1'-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

試薬・触媒・溶媒 3

HCID 91885323Palladium(2+);2-phenylaniline;tritert-butyl(chloro)phosphanium触媒HCID 679Dimethyl Sulfoxide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
25 °C

実験手順

A mixture of (3R,3aR,6R,6aR)-6-((6-chloro-5-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (40 mg, 0.072 mmol) and (2-fluoro-[1,1′-biphenyl]-4-yl)boronic acid (18.72 mg, 0.087 mmol) in anhydrous dioxane (0.4 ml) was purged with N2 and then chloro[(tri-tert-butylphosphine)-2-(2-aminobiphenyl)]palladium(II) (7.4 mg, 0.014 mmol) and tripotassium phosphate (0.217 ml, 0.217 mmol) were added under N2 flow. The mixture was stirred at 25° C. overnight. The crude mixture was extracted with DCM and the combined organic extracts were washed with water and evaporated under reduced pressure. 1 ml of 1:1 CH2Cl2 and TFA was added to the resulting residue and the reaction mixture was stirred for 2 hours. Then the solvent was evaporated under reduced pressure to give an amber residue. The residue was diluted with 1.5 ml DMSO, filtered and purified by mass directed reverse phase column chromatography eluting with acetonitrile/water+0.1% TFA to give the title product. LC-MS: calculated for C24H19ClFN3O4, 467.10, observed m/e: 468.11 (M+H)+ (RT 0.76/2.00 min).

後処理

  1. customwas purged with N2
  2. extractionThe crude mixture was extracted with DCM
  3. washthe combined organic extracts were washed with water
  4. customevaporated under reduced pressure
  5. addition1 ml of 1:1 CH2Cl2 and TFA was added to the resulting residue
  6. stirringthe reaction mixture was stirred for 2 hours
  7. customThen the solvent was evaporated under reduced pressure
  8. customto give an amber residue
  9. filtrationfiltered
  10. custompurified by mass
  11. washeluting with acetonitrile/water+0.1% TFA

出典と根拠

ORDレコード
ord-b91a81b20d904096a77743f119e11b84
出典データセット
uspto-grants-2016_03
特許番号
US09290517B2

反応ノート

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