Hydrochloric Acid → 4-(7-Benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile hydrochloride

HRID 15416Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 15416
C(N1C(=O)C(C2C=CC(C#N)=CC=2)N2C=NC=C2C1)C1C=CC=CC=1.[CH2:26]([N:33]1[C:38](=[O:39])[C:37]([C:41]2[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[CH:43][CH:42]=2)([CH3:40])[N:36]2[CH:49]=[N:50][CH:51]=[C:35]2[CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CI.[ClH:64]>C1COCC1.CC(C)=O.C(OCC)C>[ClH:64].[CH2:26]([N:33]1[C:38](=[O:39])[C:37]([C:41]2[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[CH:43][CH:42]=2)([CH3:40])[N:36]2[CH:49]=[N:50][CH:51]=[C:35]2[CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 9927427HCID 9927427, VerbindungHCID 100659784-(7-Benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile

Produkt 1

HCID 179756504-(7-Benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 180AcetoneLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of the title compound of Example 3, 4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile (0.24 g, 0.63 mmol) in 5 mL of THF at −78° C. is added LHMDS (0.70 mL, 0.70 mmol) and the resulting solution is stirred for 15 min. To this solution is added methyl iodide (0.040 mL, 0.67 mmol) and the solution is stirred for 15 min, then warmed gradually to RT. The reaction mixture is quenched by addition of NH4Cl and extracted with EtOAc. The organic solution is washed with brine, dried (anhydrous sodium sulfate) and evaporated to an oil. Purification by flash chromatography (silica gel) eluting with EtOAc:MeOH:NH4OH (95:5:0.5) gives the free base which is dissolved in acetone and HCl (g) in diethyl ether is added to afford 4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile hydrochloride: m.p. 230-232° C.; 1H-NMR (DMSO-d6) δ 9.54 (1H, s), 7.90 (2H, d, J=8.7), 7.74 (1H, s), 7.32 (3H, m), 7.22 (2H, d, J=8.7), 7.15 (2H, m), 4.73 (1H, d, J=16.9), 4.71 (1H, d, J=14.6), 4.66 (1H, d, J=14.6), 4.12 (1H, d, J=16.9), 2.25 (3H, s); 13C-NMR (DMSO-d6) δ 163.1, 141.1, 133.8, 132.3, 131.3, 126.8, 125.8, 125.7, 124.0, 123.7, 116.2, 114.2, 110.0, 64.6, 48.4, 38.5, 22.6; e/z (ES) 343 (M+1, 100%); calculated for C21H18N4O HCl, C, 66.58; H, 5.05; N, 14.79. found C, 66.41; H, 5.01; N, 14.80.

Aufarbeitung

  1. stirringthe solution is stirred for 15 min
  2. customThe reaction mixture is quenched by addition of NH4Cl
  3. extractionextracted with EtOAc
  4. washThe organic solution is washed with brine
  5. dry with materialdried (anhydrous sodium sulfate)
  6. customevaporated to an oil
  7. customPurification by flash chromatography (silica gel)
  8. washeluting with EtOAc:MeOH:NH4OH (95:5:0.5)
  9. customgives the free base which

Quellen und Nachweise

ORD-Eintrag
ord-c9d96de60032466ba0c0b3b5fba39207
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732603B2

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