Potassium Phosphate, Tribasic → HCID 90009295, 화합물

HRID 531279

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HRID 531279 반응식
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[C:27]([O:41][CH3:42])=[N:28][CH:29]=[C:30](B5OC(C)(C)C(C)(C)O5)[CH:31]=4)=[CH:24][N:23]=[C:22]([S:43][CH3:44])[N:21]=3)[C@H:14]2[CH3:45])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Br[C:49]1[C:50]([CH3:55])=[N:51][NH:52][C:53]=1[CH3:54].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[Na+].O.C(OCC)(=O)C>[Pd](Cl)Cl.O.C1COCC1>[F:47][C:2]([F:46])([F:1])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[C:27]([O:41][CH3:42])=[N:28][CH:29]=[C:30]([C:49]5[C:50]([CH3:55])=[N:51][NH:52][C:53]=5[CH3:54])[CH:31]=4)=[CH:24][N:23]=[C:22]([S:43][CH3:44])[N:21]=3)[C@H:14]2[CH3:45])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 769374-bromo-3,5-dimethyl-1H-pyrazoleHCID 90009192HCID 90009192, 화합물HCID 131718255Brine ethyl acetate

생성물 1

HCID 90009295HCID 90009295, 화합물

시약·촉매·용매 3

HCID 24290Palladium Chloride촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-({5-[2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-2-(methylthio)pyrimidin-4-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (Step A, 0.76 g, 1.11 mmol), 4-bromo-3,5-dimethyl-1H-pyrazole (0.233 g, 1.33 mmol), tripotassium phosphate (1.178 g, 5.50 mmol), (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) chloride (XPHOS Biphenyl Precatalyst) (0.087 g, 0.11 mmol), THF (8.33 mL), and H2O (2.77 mL) were sealed in a microwave vessel and subject to microwave irradiation at 120° C. for 1.5 hrs. The resulting reaction mixture was worked up with brine/ethyl acetate. The combined extracts were dried over Na2SO4, filtered and evaporated to afford a brown mixture. This mixture was purified by flash chromatography (SiO2, ISCO, RediSep 24 g Cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 50% ethyl acetate). Related fractions were pooled and evaporated under reduced pressure to afford an off-white solid of 450 mg as the titled compound. LCMS (M+H)+: 653.35.

후처리

  1. customsubject to microwave irradiation at 120° C. for 1.5 hrs
  2. customThe resulting reaction mixture
  3. dry with materialThe combined extracts were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford a brown mixture
  7. customThis mixture was purified by flash chromatography (SiO2, ISCO, RediSep 24 g Cartridge)
  8. washThe column was eluted by an ethyl acetate/hexanes mixture (0% to 50% ethyl acetate)
  9. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-38bdaac62f984c738726d153d8a728d3
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09353101B2

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