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Sodium Carbonate → (S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4'-fluoro-2'-((S)-pent-4-en-2-yloxy)-[1,1'-biphenyl]-3-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

HRID 1482000
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HRID 1482000 반응식
[CH2:1]([O:4][C:5]1([CH3:38])[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[CH:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:29]([O:31][CH3:32])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[F:39][C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[C:42]([O:49][C@H:50]([CH2:52][CH:53]=[CH2:54])[CH3:51])[CH:41]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.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>[CH2:1]([O:4][C:5]1([CH3:38])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:43]5[CH:44]=[CH:45][C:40]([F:39])=[CH:41][C:42]=5[O:49][C@H:50]([CH2:52][CH:53]=[CH2:54])[CH3:51])[CH:23]=[CH:24][CH:25]=4)[N:19]=[C:15]3[CH:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:29]([O:31][CH3:32])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]
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참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 118308811(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetateHCID 123945833(S)-(4-Fluoro-2-(pent-4-en-2-yloxy)phenyl)boronic acid

생성물 1

HCID 118308907(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4'-fluoro-2'-((S)-pent-4-en-2-yloxy)-[1,1'-biphenyl]-3-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate
수율 66.5%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

To a solution of (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate (0.27 g, 0.462 mmol, 1 equiv) and (S)-(4-fluoro-2-(pent-4-en-2-yloxy)phenyl)boronic acid (207 mg, 0.924 mmol, 2 equiv) in DMF (5 mL, sparged with nitrogen for 10 min) was added Pd(PPh3)4 (53 mg, 0.046 mmol, 0.1 equiv) and 2 M Na2CO3 (0.46 mL, 0.924 mmol, 2 equiv). The reaction was heated at 90° C. for 2.5 h. Upon cooling to ambient temperature, the reaction was diluted with EtOAc, washed with water, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (210 mg, 66%) as a viscous yellow oil. LCMS (ESI, M+1): 684.35.

후처리

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

출처 및 근거

ORD 기록
ord-cf9e4a91bc9c4ee3ae6cdb0965f7e3da
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09409922B2

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