Hydrochloric Acid → 4-(5-Aminomethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one

HRID 1690741Notes

Reaction equation

HRID 1690741 reaction equation
[CH3:1][C:2]1([CH3:20])[CH:11]([N:12]2[C:16]([C:17]#[N:18])=[CH:15][N:14]=[CH:13]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:19])[O:3]1.Cl.CO>C1COCC1>[NH2:18][CH2:17][C:16]1[N:12]([CH:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4](=[O:19])[O:3][C:2]2([CH3:20])[CH3:1])[CH:13]=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 24805168HCID 24805168, compound

Product 1

HCID 577811204-(5-Aminomethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The solution of 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carbonitrile (0.130 g, 0.5 mmol) (Example 20) in THF (2 mL) is added borane dimethyl sulfide complex (0.055 mL, 0.55 mmol) dropwise, and the resulting mixture is stirred at reflux for 30 min. The reaction mixture is concentrated in vacuo and the residue is redissolved in THF (2 mL) and 0.5 M hydrogen chloride in methanol (1.1 mL, 0.55 mmol) is added dropwise. The reaction mixture is stirred at ambient temperature for 1.5 h. The mixture is concentrated in vacuo and the residue is purified by semi-preparative reverse phase HPLC to give 4-(5-aminomethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one as a yellowish solid; MS (ESI) m/z 271.9 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 3 H), 1.59 (s, 3 H), 4.55-4.74 (m, 2 H), 5.99 (s, 1 H), 7.67-7.76 (m, 3 H), 7.82 (td, J=7.6, 1.5 Hz, 1 H), 8.29 (dd, J=7.7, 1.4 Hz, 1H), 8.52 (br. s, 1 H)

Workup

  1. temperatureat reflux for 30 min
  2. concentrationThe reaction mixture is concentrated in vacuo
  3. dissolutionthe residue is redissolved in THF (2 mL)
  4. stirringThe reaction mixture is stirred at ambient temperature for 1.5 h
  5. concentrationThe mixture is concentrated in vacuo
  6. customthe residue is purified by semi-preparative reverse phase HPLC

Sources & evidence

ORD record
ord-14049ed1fe6446a1a1a0e30fa59f62bc
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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