Cesium carbonate → ethyl 5-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

HRID 1043943ノート

反応式

HRID 1043943 の反応式
I[C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([O:9][CH3:10])[C:3]=1[CH3:11].C(=O)([O-])[O-].[Cs+].[Cs+].[F:18][C:19]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:22]=[CH:21][C:20]=1[C:34]1[N:38]([C@H:39]2[CH2:43][CH2:42][O:41][CH2:40]2)[N:37]=[CH:36][C:35]=1[C:44]([O:46][CH2:47][CH3:48])=[O:45].COC1C=C(OC)C=CC=1CN1C2C=C(B(O)O)C=CC=2C2N(C3CCOCC3)N=CC=2C1=O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:18][C:19]1[CH:24]=[C:23]([C:2]2[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([O:9][CH3:10])[C:3]=2[CH3:11])[CH:22]=[CH:21][C:20]=1[C:34]1[N:38]([C@H:39]2[CH2:43][CH2:42][O:41][CH2:40]2)[N:37]=[CH:36][C:35]=1[C:44]([O:46][CH2:47][CH3:48])=[O:45]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 86686332HCID 86686332、化合物HCID 86686369[5-(2,4-dimethoxybenzyl)-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]boronic acidHCID 86686374Ethyl (S)-5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-(tetrahydrofuran-3-yl)-1H-pyrazole-4-carboxylate

生成物 1

HCID 86686373ethyl 5-[2-fluoro-4-(2-methoxy-3,5-dimethylpyridin-4-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

Water (170 mL), 4-iodo-2-methoxy-3,5-dimethylpyridine obtained in Preparation Example 29(3) (35.6 g), Pd(PPh3)4 (6.52 g) and cesium carbonate (110 g) were added to a solution of ethyl 5-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate obtained in Preparation Example 6 (51.9 g) in 1,4-dioxane (500 mL), and the reaction mixture was reacted at 110° C. for six hours. The reaction mixture was returned to room temperature, and the organic layer was then separated. The organic layer was concentrated under reduced pressure. The aqueous layer, ethyl acetate (700 m) and water (100 mL) were added to the resulting residue, and the organic layer was separated. The aqueous layer was re-extracted with ethyl acetate (50 mL). The combined organic layers were sequentially washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane, 5% to 14%). The product was then purified again by NH silica gel column chromatography (ethyl acetate/n-heptane, 2% to 10%) to give the title compound (435 g).

後処理

  1. customthe reaction mixture was reacted at 110° C. for six hours
  2. customwas returned to room temperature
  3. customthe organic layer was then separated
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. additionThe aqueous layer, ethyl acetate (700 m) and water (100 mL) were added to the resulting residue
  6. customthe organic layer was separated
  7. extractionThe aqueous layer was re-extracted with ethyl acetate (50 mL)
  8. washThe combined organic layers were sequentially washed with water and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane, 5% to 14%)
  13. customThe product was then purified again by NH silica gel column chromatography (ethyl acetate/n-heptane, 2% to 10%)

出典と根拠

ORDレコード
ord-1359e80a76fa4846bb408d4126bd84d5
出典データセット
uspto-grants-2013_10
特許番号
US08563565B2

反応ノート

読み込み中…