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

HRID 896352Notes

Reaction equation

HRID 896352 reaction equation
C(O[C:6](=O)[N:7]([CH2:9][C:10]1[CH:39]=[CH:38][C:13]2[N:14]([CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36])[C:15]([CH2:17][N:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:21](=[O:28])[N:20]([CH:29]4[CH2:31][CH2:30]4)[C:19]3=[O:32])=[N:16][C:12]=2[CH:11]=1)C)(C)(C)C.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O.C(Cl)(=O)C>C(Cl)Cl>[CH:29]1([N:20]2[C:21](=[O:28])[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:18]([CH2:17][C:15]3[N:14]([CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36])[C:13]4[CH:38]=[CH:39][C:10]([CH2:9][NH:7][CH3:6])=[CH:11][C:12]=4[N:16]=3)[C:19]2=[O:32])[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 6422Trifluoroacetic acid2×HCID 7519AnisoleHCID 69718845HCID 69718845, compound

Product 1

HCID 208140493-cyclopropyl-1-[5-methylaminomethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-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]-methyl-carbamic acid tert-butyl ester (39 mg, 0.071 mmol) and anisole (77 μL, 0.71 mmol) in DCM (3 mL) was added TFA (165 μL, 2.14 mmol). The solution was allowed to reach room temperature and after 1 h another amount of TFA (200 μL) was added. After 1 h the volatiles were removed in vacuo and the residue was stripped with DCM (2×) and methanol (1×). The TFA salt was dissolved in methanol followed by the addition of acetyl cloride (50 μL, 0.71 mmol) and concentrated. This procedure was repeated once. The product was triturated in diethyl ether to give 3-cyclopropyl-1-[5-methylaminomethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-1H-quinazoline-2,4-dione; HCl salt (31 mg, 91%) as an off white solid.

Workup

  1. customAfter 1 h the volatiles were removed in vacuo
  2. dissolutionThe TFA salt was dissolved in methanol
  3. concentrationconcentrated
  4. customThe product was triturated in diethyl ether

Sources & evidence

ORD record
ord-61f4beaa97894defb778b2b9ca1133d8
Source dataset
uspto-grants-2005_07
Patent number
US06919331B2

Reaction notes

Loading…