Pyridine → 3,3-dimethyl-N-((6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide

HRID 1049326Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1049326
[CH3:1][C:2]1([CH3:9])[CH2:5][CH:4]([C:6]([NH2:8])=[O:7])[CH2:3]1.C(Cl)(=O)[C:11](Cl)=[O:12].[CH3:16][C:17]1[N:22]=[C:21]([NH2:23])[CH:20]=[CH:19][C:18]=1[O:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([C:31]2[O:35][N:34]=[C:33]([CH3:36])[CH:32]=2)[CH:26]=1.N1C=CC=CC=1>ClCCCl.C1COCC1>[CH3:1][C:2]1([CH3:9])[CH2:5][CH:4]([C:6]([NH:8][C:11](=[O:12])[NH:23][C:21]2[CH:20]=[CH:19][C:18]([O:24][C:25]3[CH:30]=[CH:29][N:28]=[C:27]([C:31]4[O:35][N:34]=[C:33]([CH3:36])[CH:32]=4)[CH:26]=3)=[C:17]([CH3:16])[N:22]=2)=[O:7])[CH2:3]1

Komponenten

7

Edukt 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 5229333,3-Dimethylcyclobutane-1-carboxamideHCID 904036286-Methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine

Produkt 1

HCID 862676413,3-dimethyl-N-((6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamideAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
83 °C

Versuchsvorschrift

A solution of Example B1 (0.028 g, 0.221 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.019 mL, 0.221 mmol), heated at 83° C. for 2 h, cooled to RT, added drop-wise to a solution of Example A7 (0.052 g, 0.184 mmol) and pyridine (0.074 mL, 0.921 mmol) in THF (4.0 mL) and stirred at RT for 2 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over MgSO4 and concentrated to dryness. The resulting material was treated with MeCN and the solid collected via filtration and dried to afford 3,3-dimethyl-N-((6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide (51 mg, 64%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.08 (s, 1H), 10.70 (s, 1H), 8.56 (d, J=5.7 Hz, 1H), 7.92 (d, J 8.8 Hz, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.35 (d, J=2.5 Hz, 1H), 6.98-6.95 (m, 2H), 3.25 (m, 1H), 2.28 (s, 3H), 2.26 (s, 3H), 2.02-1.88 (m, 4H), 1.13 (s, 3H), 1.05 (s, 3H); MS (ESI) m/z: 436.2 (M+H+).

Aufarbeitung

  1. temperaturecooled to RT
  2. additionThe mixture was treated with satd
  3. extractionNaHCO3, extracted with EtOAc (3×)
  4. dry with materialthe combined organics were dried over MgSO4
  5. concentrationconcentrated to dryness
  6. additionThe resulting material was treated with MeCN
  7. filtrationthe solid collected via filtration
  8. customdried

Quellen und Nachweise

ORD-Eintrag
ord-8d1e2e32965e44e4ae62aa536bf126be
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09382228B2

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