1,2-Dichloroethane → HCID 46215629, Verbindung

HRID 62543

Reaktionsgleichung

Reaktionsgleichung von HRID 62543
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:20]=2[C:21](O)=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1.C1C=CC2[N:37]([OH:38])N=NC=2C=1.[CH2:39](Cl)CCl.CCN(C(C)C)C(C)C>CN(C)C=O.C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([NH:18][C:19]2[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:20]=2[C:21]([NH:37][O:38][CH3:39])=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:15])[CH3:16])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1

Komponenten

8

Edukt 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667695202-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzoic acid

Produkt 1

HCID 46215629HCID 46215629, VerbindungAusbeute 30,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzoic acid (3.2 g, 7.92 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added HOBT (1.456 g, 9.51 mmol) and EDC (1.823 g, 9.51 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (0.794 g, 9.51 mmol). After 30 min the reaction mixture was cooled to 0° C. and DIEA (4.14 mL, 23.77 mmol) was added. The reaction mixture was stirred at the room temperature 24 hr. Water (100 mL) was added followed by acetic acid (1 mL) and the solution was extracted with 2×50 ml of ethyl acetate. The combined organic layers were washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The oil was suspended in dichloromethane and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluoro-N-(methyloxy)benzamide (1.1 g, 2.414 mmol, 30.5% yield) was isolated as a white solid; 1H NMR (400 MHz, DMSO-d6) ppm 1.24 (d, J=6.57 Hz, 6 H) 2.08 (s, 3 H) 3.68 (s, 3 H) 4.33 (quin, J=6.57 Hz, 1 H) 5.83 (d, J=5.05 Hz, 1 H) 5.84 (s, 1 H) 7.30-7.49 (m, 2 H) 7.49-7.63 (m, 1 H) 7.92 (s, 1 H) 8.41 (d, J=4.29 Hz, 2 H) 11.85 (s, 1 H); HPLC Rt=2.18 min, MS (ESI): 433.3 [M+H]+.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at the room temperature 24 hr
  2. extractionthe solution was extracted with 2×50 ml of ethyl acetate
  3. washThe combined organic layers were washed with 2×50 ml
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-1328123b07264bc4a2f138af4dc2d07f
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09446034B2

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