Cesium carbonate → ethyl 5-[2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate

HRID 1043936노트

반응식

HRID 1043936 반응식
Br[C:2]1[C:3]([O:10][CH3:11])=[N:4][C:5]([CH3:9])=[CH:6][C:7]=1[CH3:8].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]([CH:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)[N:37]=[CH:36][C:35]=1[C:45]([O:47][CH2:48][CH3:49])=[O:46].BrC1C(C)=CC(C#N)=NC=1C>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:3]([O:10][CH3:11])=[N:4][C:5]([CH3:9])=[CH:6][C:7]=2[CH3:8])[CH:22]=[CH:21][C:20]=1[C:34]1[N:38]([CH:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)[N:37]=[CH:36][C:35]=1[C:45]([O:47][CH2:48][CH3:49])=[O:46]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 866863313-Bromo-2-methoxy-4,6-dimethylpyridineHCID 866863465-Bromo-4,6-dimethylpicolinonitrileHCID 86686364ethyl 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate

생성물 1

HCID 86686363ethyl 5-[2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

Water (5 mL), 3-bromo-2-methoxy-4,6-dimethylpyridine obtained in Preparation Example 26 (784 mg), Pd(PPh3)4 (380 mg) and cesium carbonate (2.36 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-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate obtained in Preparation Example 3 (2.04 g) in 1,4-dioxane (20 mL), and the reaction mixture was reacted at 110° C. for two hours in a nitrogen atmosphere. The reaction mixture was returned to room temperature and then filtered through Celite™. The filtrate was concentrated under reduced pressure. Ethyl acetate (100 mL) and water (100 mL) were added to the residue. The aqueous layer was extracted with ethyl acetate (50 mL×2). The combined organic layers were dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane, 10% to 23%). The title compound obtained by the same method (578 mg) was combined, and the combined product was purified again by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 70%) to give the title compound (2.07 g).

후처리

  1. customthe reaction mixture was reacted at 110° C. for two hours in a nitrogen atmosphere
  2. customwas returned to room temperature
  3. filtrationfiltered through Celite™
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. additionEthyl acetate (100 mL) and water (100 mL) were added to the residue
  6. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×2)
  7. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane, 10% to 23%)

출처 및 근거

ORD 기록
ord-9e8811eff6f9435faf9ecca372ad3218
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08563565B2

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