Methanol → HCID 86689753, Verbindung

HRID 1396398Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396398
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16](Cl)[N:15]=[N:14][C:13]=2[C:19]([NH2:21])=[O:20])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].CO.C(Cl)Cl>CN1C(=O)CCC1>[NH4+:10].[OH-:20].[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16]([NH:22][C@@H:23]3[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]3[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[N:15]=[N:14][C:13]=2[C:19](=[O:20])[NH2:21])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 887MethanolHCID 6344DichloromethaneHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86689752HCID 86689752, Verbindung

Produkt 2

HCID 14923Ammonium HydroxideHCID 86689753HCID 86689753, VerbindungAusbeute 78,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

A stirred solution of 4-(6-tert-butylpyridin-2-ylamino)-6-chloropyridazine-3-carboxamide (317 mg, 1.04 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (444 mg, 2.07 mmol) in NMP (4 mL) was heated at 140° C. for 24 h in a sealed tube. The mixture was concentrated in vacuo (Kuglerohr, high vacuum) to a brown solid. Purification by chromatography (silica, 40 g, 0-10% of a 9:1 MeOH solution in dichloromethane, 30 min) then a second purification by chromatography (silica, 24 g, 10% acetone in dichloromethane, 10 min, then 9:1:90 MeOH:NH4OH:DCM, 10 min) gave tert-butyl (1S,2R)-2-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (197 mg, 407 μmol, 39%) as a brown viscous gum. MS (EI/CI) m/z: 484.2 [M+H]. This material contained small amounts of residual NMP and was used directly in the next step without further purification.

Aufarbeitung

  1. concentrationThe mixture was concentrated in vacuo (Kuglerohr, high vacuum) to a brown solid
  2. customPurification by chromatography (silica, 40 g, 0-10% of a 9:1 MeOH solution in dichloromethane, 30 min)
  3. customa second purification by chromatography (silica, 24 g, 10% acetone in dichloromethane, 10 min

Quellen und Nachweise

ORD-Eintrag
ord-6bd98dd621b7426e971d27b8e80ce361
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901124B2

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