Hydrochloric Acid → [2-(3-Cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(4-hydroxy-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester

HRID 896356Notes

Reaction equation

HRID 896356 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:45]=[CH:44][C:13]2[N:14]([CH2:33][CH2:34][CH2:35][CH2:36][O:37]C(=O)C(C)(C)C)[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)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl>CO.O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1[CH:45]=[CH:44][C:13]2[N:14]([CH2:33][CH2:34][CH2:35][CH2:36][OH:37])[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)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69709395HCID 69709395, compound

Product 1

HCID 69718999[2-(3-Cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(4-hydroxy-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl esterYield 63.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 2,2-dimethyl-propionic acid 4-[5-(tert-butoxycarbonylamino-methyl)-2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-benzoimidazol-1-yl]-butyl ester (110 mg, 0.178 mmol) in methanol (5 mL) and water (1.5 mL) was added 1M NaOH (356 μL, 0.356 mmol). The resulting mixture was heated at 70-80° C. for 2 hrs. The solution was neutralized with 1M HCl, methanol was removed in vacuo and the aqueous residue extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine and dried (MgSO4). Purification by flash chromatography (eluent 2%, 5% methanol in DCM) afforded [2-(3-Cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(4-hydroxy-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester (60 mg, 63%) as a white solid.

Workup

  1. customwas removed in vacuo
  2. extractionthe aqueous residue extracted with ethyl acetate (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. customPurification by flash chromatography (eluent 2%, 5% methanol in DCM)

Sources & evidence

ORD record
ord-51e3c0f7b31648018d0b5304a7825324
Source dataset
uspto-grants-2005_07
Patent number
US06919331B2

Reaction notes

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