Triethylamine → N-(3-(4-(4-phenoxyphenoxy)pyridin-3-yl)phenyl)acrylamide

HRID 1522092노트

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HRID 1522092 반응식
[O:1]([C:8]1[CH:27]=[CH:26][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=2)[NH2:22])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:35](Cl)(=[O:38])[CH:36]=[CH2:37]>CN1CCCC1=O.ClCCl>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:20]=[C:21]([NH:22][C:35](=[O:38])[CH:36]=[CH2:37])[CH:23]=[CH:24][CH:25]=2)=[CH:26][CH:27]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 13140Acryloyl chlorideHCID 714740103-(4-(4-Phenoxyphenoxy)pyridin-3-yl)aniline

생성물 1

HCID 86721736N-(3-(4-(4-phenoxyphenoxy)pyridin-3-yl)phenyl)acrylamide수율 36.7%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 13387N-methyl-2-pyrrolidone용매

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온도
0 °C

실험 절차

Into a 20 mL vial was placed 3-(4-(4-phenoxyphenoxy)pyridin-3-yl)aniline (30.00 mg, 0.08 mmol), N,N-diethylethanamine (0.02 mL, 0.17 mmol) suspended in 1-methylpyrrolidin-2-one (0.35 mL) and dichloromethane (2.00 mL). The resulting mixture was cooled to 0° C. Added acryloyl chloride (0.02 mL, 0.25 mmol). The ice bath was left to melt and the reaction mixture was stirred at rt overnight. The reaction mixture was purified using Biotage column chromatography eluting 0-40% MeOH in EtOAc. Fractions containing the desired product were combined and concentrated. Purified using prep-HPLC eluting 25-55% CH3CN in 0.1% TFA in H2O. Fractions containing the desired product were combined and lyophilized overnight to afford N-(3-(4-(4-phenoxyphenoxy)pyridin-3-yl)phenyl)acrylamide as a white solid (12.00 mg, 35% yield). HPLC purity: 100%, RT=4.235 min. MS: m/z=409 [M+H]+, RT=3.38 min. 1H-NMR (DMSO-d6) δ 10.23 (s, 1H), 8.52 (s, 1H), 8.43 (d, 1H), 7.95 (s, 1H), 7.71 (d, 1H), 7.44-7.33 (m, 4H), 7.19 (d, 2H), 7.13 (t, 1H), 7.09 (d, 2H), 7.02 (d, 2H), 6.80 (d, 1H), 6.45 (dd, 1H), 6.26 (d, 1H), 5.75 (d, 1H).

후처리

  1. customThe reaction mixture was purified
  2. washeluting 0-40% MeOH in EtOAc
  3. additionFractions containing the desired product
  4. concentrationconcentrated
  5. customPurified
  6. washusing prep-HPLC eluting 25-55% CH3CN in 0.1% TFA in H2O
  7. additionFractions containing the desired product
  8. waitlyophilized overnight

출처 및 근거

ORD 기록
ord-255757d2718e4781b3ba2f4fe2a23884
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073947B2

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