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

HRID 15416Notes

Reaction equation

HRID 15416 reaction equation
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

Participants

9

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-c9d96de60032466ba0c0b3b5fba39207
Source dataset
uspto-grants-2010_06
Patent number
US07732603B2

Reaction notes

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