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 1482082노트

반응식

HRID 1482082 반응식
[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]

참가 물질

9

반응물 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

생성물 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)acetate수율 84%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-192519e15c9f460babbc21f33e534b84
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409922B2

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