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

HRID 1522092Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1522092
[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

Komponenten

6

Edukt 3

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

Produkt 1

HCID 86721736N-(3-(4-(4-phenoxyphenoxy)pyridin-3-yl)phenyl)acrylamideAusbeute 36,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-255757d2718e4781b3ba2f4fe2a23884
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073947B2

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