Potassium Phosphate, Tribasic → (S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4',5'-difluoro-2'-((S)-pent-4-en-2-yloxy)-[1,1'-biphenyl]-3-yl)-7,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

HRID 1482082Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1482082
[CH2:1]([O:4][C:5]1([CH3:39])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22](Br)[CH:21]=4)[N:19]=[C:15]3[C:14]([CH3:27])=[C:13]([CH3:28])[C:12]=2[C@H:29]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:30]([O:32][CH3:33])=[O:31])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[F:69][C:70]1[C:75]([F:76])=[CH:74][C:73](B2OC(=O)CN(C)CC(=O)O2)=[C:72]([O:88][C@H:89]([CH2:91][CH:92]=[CH2:93])[CH3:90])[CH:71]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:4][C:5]1([CH3:39])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:73]5[CH:74]=[C:75]([F:76])[C:70]([F:69])=[CH:71][C:72]=5[O:88][C@H:89]([CH2:91][CH:92]=[CH2:93])[CH3:90])[CH:23]=[CH:24][CH:25]=4)[N:19]=[C:15]3[C:14]([CH3:27])=[C:13]([CH3:28])[C:12]=2[C@H:29]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:30]([O:32][CH3:33])=[O:31])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Komponenten

9

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 118308864(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetateHCID 131736668(S)-2-(4,5-difluoro-2-(pent-4-en-2-yloxy)phenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione

Produkt 1

HCID 118308836(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4',5'-difluoro-2'-((S)-pent-4-en-2-yloxy)-[1,1'-biphenyl]-3-yl)-7,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetateAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate (0.25 g, 0.42 mmol, 1 equiv), Sphos (34 mg, 0.084 mmol, 0.2 equiv), (S)-2-(4,5-difluoro-2-(pent-4-en-2-yloxy)phenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (0.18 g, 0.52 mmol, 1.25 equiv), K3PO4 (1.05 g, 4.59 mmol, 11 equiv), and Pd(OAc)2 (9 mg, 0.042 mmol, 0.1 equiv) in dioxane (5 mL) and water (1 mL) was heated at 80° C. for 1.5 h. Upon cooling to ambient temperature, the reaction mixture was diluted with EtOAc, washed with saturated aqueous sodium bicarbonate, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by silica gel flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (0.25 g, 84%) as a white solid. LCMS (ESI, M+1): 716.70.

Aufarbeitung

  1. temperatureUpon cooling to ambient temperature
  2. washwashed with saturated aqueous sodium bicarbonate
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel flash column chromatography (0-100% EtOAc [2% TEA]/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-192519e15c9f460babbc21f33e534b84
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409922B2

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