1,4-Dioxane → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 531230노트

반응식

HRID 531230 반응식
O1CCOCC1.[F:7][C:8]([F:45])([F:44])[C:9]1[CH:10]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[N:21]([CH2:25][C:26]3[C:31](B4OC(C)(C)C(C)(C)O4)=[CH:30][N:29]=[C:28]([S:41][CH3:42])[N:27]=3)[C@H:20]2[CH3:43])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.Br[C:47]1[C:48]([O:54][CH3:55])=[N:49][CH:50]=[C:51]([Cl:53])[CH:52]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.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>[F:17][C:15]([F:16])([F:18])[C:13]1[CH:12]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[N:21]([CH2:25][C:26]3[C:31]([C:47]4[C:48]([O:54][CH3:55])=[N:49][CH:50]=[C:51]([Cl:53])[CH:52]=4)=[CH:30][N:29]=[C:28]([S:41][CH3:42])[N:27]=3)[C@H:20]2[CH3:43])[CH:10]=[C:9]([C:8]([F:7])([F:44])[F:45])[CH:14]=1

참가 물질

7

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 135677513-Bromo-5-chloro-2-methoxypyridineHCID 90009110(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylsulfanyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one2회

생성물 1

HCID 118021383(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6342Acetonitrile용매

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온도
170 °C

실험 절차

A dioxane (17.3 mL) solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylsulfanyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one (INTERMEDIATE 21, 2.0 g, 3.46 mmol), 3-bromo-5-chloro-2-methoxypyridine (0.925 g, 4.16 mmol) and 2M potassium phosphate tribasic (3.5 mL, 7.00 mmol) in a microwave vial was evacuated and charged three times with nitrogen. Then Pd(Ph3P)4 (0.400 g, 0.346 mmol) was added and the reaction vial was capped. The reaction was stirred for 10 minutes at 170° C. in a microwave reactor. LCMS showed complete conversion to the product. The reaction was diluted with acetonitrile (5 mL) and filtered through a 2 g plug of RP C18 silica, rinsing with 10 mL acetonitrile. The filtrate was concentrated and the crude was purified by silica gel chromatography, eluting with a gradient of 0-50% ethyl acetate/hexanes to give the title compound as a pale yellow foam. LCMS (M+H)+: 593.3

후처리

  1. additioncharged three times with nitrogen
  2. customthe reaction vial was capped
  3. filtrationfiltered through a 2 g plug of RP C18 silica
  4. washrinsing with 10 mL acetonitrile
  5. concentrationThe filtrate was concentrated
  6. customthe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-50% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-6c437d4075684bf6bea1585d2eed4564
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09353101B2

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