HOAt → (R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

HRID 1514372Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1514372
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]1[N:9]=[N:10][C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=12.[F:24][C:25]1([F:34])[CH2:30][CH2:29][CH:28]([C:31](O)=[O:32])[CH2:27][CH2:26]1.Cl.C(N=C=NCCCN(C)C)C.N1C2C(=NC=CC=2)N(O)N=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C.CCCCCC>[F:24][C:25]1([F:34])[CH2:30][CH2:29][CH:28]([C:31]([N:6]2[CH2:5][CH2:4][N:3]([C:8]3[N:9]=[N:10][C:11]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[C:12]4[CH:17]=[CH:16][N:15]=[CH:14][C:13]=34)[C@H:2]([CH3:1])[CH2:7]2)=[O:32])[CH2:27][CH2:26]1

Komponenten

9

Edukt 5

HCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27791364,4-Difluorocyclohexanecarboxylic acidHCID 57657605(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine

Produkt 1

HCID 25226575(R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8058HexaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine 16 (150 mg, 491 μmol), 4,4-difluorocyclohexanecarboxylic acid (88.7 mg, 540 μmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (113 mg, 589 μmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (80.2 mg, 589 μmol), sodium bicarbonate (82.5 mg, 982 μmol) were stirred in DMF (3 ml) for one hour. The reaction was then taken up in ethyl acetate (30 ml) and washed with aqueous K2CO3 (10%), water, and brine. The organic phase was dried (MgSO4) and evaporated to give an orange oil. Chromatography of the residue over silica with a gradient of hexane to 100% ethyl acetate gave (R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone 17 as a yellow solid. LC/MS m/z=452 (M+H+).

Aufarbeitung

  1. washwashed with aqueous K2CO3 (10%), water, and brine
  2. dry with materialThe organic phase was dried (MgSO4)
  3. customevaporated
  4. customto give an orange oil

Quellen und Nachweise

ORD-Eintrag
ord-b3d779c93b384f2e904585bed1589a9a
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08222251B2

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