Cesium carbonate → (+/-)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

HRID 1043942ノート

反応式

HRID 1043942 の反応式
COC1C=C(OC)C=CC=1C[N:6]1[C:15]2[CH:14]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:12]=[CH:11][C:10]=2[C:9]2[N:25]([CH:28]3[CH2:32][CH2:31][O:30][CH2:29]3)[N:26]=[CH:27][C:8]=2[C:7]1=[O:33].Cl.O1CC(NN)COCC1.Br[C:51]1[C:56]([CH3:57])=[CH:55][N:54]=[C:53]([O:58][CH3:59])[C:52]=1[CH3:60].C(=O)([O-])[O-].[Cs+].[Cs+]>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.O1CCOCC1>[CH3:59][O:58][C:53]1[C:52]([CH3:60])=[C:51]([C:13]2[CH:12]=[CH:11][C:10]3[C:9]4[N:25]([CH:28]5[CH2:32][CH2:31][O:30][CH2:29]5)[N:26]=[CH:27][C:8]=4[C:7](=[O:33])[NH:6][C:15]=3[CH:14]=2)[C:56]([CH3:57])=[CH:55][N:54]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 678116844-Bromo-2-methoxy-3,5-dimethylpyridineHCID 86686315(1,4-Dioxepan-6-yl)hydrazine hydrochlorideHCID 86686372HCID 86686372、化合物

生成物 1

HCID 136387812(+/-)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

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

反応条件

温度
70 °C

実験手順

A mixture of (±)-5-(2,4-dimethoxybenzyl)-1-(tetrahydrofuran-3-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one obtained in Preparation Example 5 (219 mg), 4-bromo-2-methoxy-3,5-dimethylpyridine obtained in Preparation Example 28 (134 mg), Pd(PPh3)4 (23.8 mg) and cesium carbonate (403 mg) was reacted in a mixed solvent of 1,4-dioxane (8 mL) and water (2 mL) using a microwave reactor at 130° C. for 70 minutes. The reaction mixture was cooled to mom temperature and then directly purified by silica gel column chromatography (ethyl acetate/n-heptane, 10% to 90%). The resulting coupling product was dissolved in TFA (4 mL), and the mixture was stirred at 70° C. for two hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. A saturated aqueous sodium bicarbonate solution was added to the residue, followed by extraction with ethyl acetate. The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (DCM, 100%, then ethyl acetate/n-heptane, 50% to 100%) to give the title compound (78 mg).

後処理

  1. customat 130° C.
  2. customfor 70 minutes
  3. temperatureThe reaction mixture was cooled to mom temperature
  4. customdirectly purified by silica gel column chromatography (ethyl acetate/n-heptane, 10% to 90%)
  5. dissolutionThe resulting coupling product was dissolved in TFA (4 mL)
  6. temperatureThe reaction mixture was cooled to room temperature
  7. concentrationconcentrated under reduced pressure
  8. additionA saturated aqueous sodium bicarbonate solution was added to the residue
  9. extractionfollowed by extraction with ethyl acetate
  10. concentrationThe organic layer was concentrated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (DCM, 100%

出典と根拠

ORDレコード
ord-93d182153a9848dbbb6ec4e66fd872d0
出典データセット
uspto-grants-2013_10
特許番号
US08563565B2

反応ノート

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