Acetyl chloride → 1-[5-aminomethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-3-cyclopropyl-1H-quinazoline-2,4-dione

HRID 896347Notes

Reaction equation

HRID 896347 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[CH:38]=[CH:37][C:12]2[N:13]([CH2:32][CH2:33][CH:34]([CH3:36])[CH3:35])[C:14]([CH2:16][N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20](=[O:27])[N:19]([CH:28]4[CH2:30][CH2:29]4)[C:18]3=[O:31])=[N:15][C:11]=2[CH:10]=1)(C)(C)C.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O.C(Cl)(=O)C>C(Cl)Cl>[NH2:7][CH2:8][C:9]1[CH:38]=[CH:37][C:12]2[N:13]([CH2:32][CH2:33][CH:34]([CH3:35])[CH3:36])[C:14]([CH2:16][N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20](=[O:27])[N:19]([CH:28]4[CH2:29][CH2:30]4)[C:18]3=[O:31])=[N:15][C:11]=2[CH:10]=1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 69718855[2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(3-methyl-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester

Product 1

HCID 208139961-[5-aminomethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-3-cyclopropyl-1H-quinazoline-2,4-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled (0° C.) solution of [2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(3-methyl-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester (34 mg, 0.064 mmol) and anisole (70 μL, 0.64 mmol) in DCM (2 mL) was added TFA (148 μL, 1.92 mmol). The solution was allowed to reach room temperature and concentrated after 4 h. The residue was stripped with DCM (2×) and methanol (1×). The TFA salt was dissolved in methanol followed by the addition of acetyl cloride (46 μL, 0.64 mmol). After 10 min the solution was concentrated in vacuo and stripped with methanol (2×) and dichloromethane (2×) to give 1-[5-aminomethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-3-cyclopropyl-1H-quinazoline-2,4-dione; HCl salt (24 mg, 80%) as an off white solid.

Workup

  1. customto reach room temperature
  2. concentrationconcentrated after 4 h
  3. dissolutionThe TFA salt was dissolved in methanol
  4. concentrationAfter 10 min the solution was concentrated in vacuo

Sources & evidence

ORD record
ord-64573c6372584f7aa8ca90449b79fa85
Source dataset
uspto-grants-2005_07
Patent number
US06919331B2

Reaction notes

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