Hydrochloric Acid → (3r)-1-Butyl-2,5-dioxo-3-((1r)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-(n-hydroxycarbamoyl)phenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

HRID 1826921Notes

Reaction equation

HRID 1826921 reaction equation
[ClH:1].[CH2:2]([N:6]1[C:11]2([CH2:16][CH2:15][N:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][C:28]([C:31]([OH:33])=O)=[CH:27][CH:26]=4)=[CH:20][CH:19]=3)[CH2:13][CH2:12]2)[C:10](=[O:34])[NH:9][C@H:8]([C@H:35]([OH:42])C2CCCCC2)[C:7]1=[O:43])[CH2:3][CH2:4][CH3:5].COC([O:49][NH2:50])(C)C.C(N(C(C)C)CC)(C)C.Cl.C(N=C=NCCCN(C)C)C.ON1[C:77]2[CH:78]=[CH:79][CH:80]=[CH:81][C:76]=2N=N1.Cl>CN(C)C=O.O>[ClH:1].[CH2:2]([N:6]1[C:11]2([CH2:16][CH2:15][N:14]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([O:24][C:25]4[CH:26]=[CH:27][C:28]([C:31](=[O:33])[NH:50][OH:49])=[CH:29][CH:30]=4)=[CH:22][CH:23]=3)[CH2:13][CH2:12]2)[C:10](=[O:34])[NH:9][C@H:8]([C@H:35]([OH:42])[CH:76]2[CH2:77][CH2:78][CH2:79][CH2:80][CH2:81]2)[C:7]1=[O:43])[CH2:3][CH2:4][CH3:5]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6918686Aplaviroc HydrochlorideHCID 13608208O-(2-Methoxyisopropyl)hydroxylamine

Product 1

HCID 23577391(3r)-1-Butyl-2,5-dioxo-3-((1r)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-(n-hydroxycarbamoyl)phenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochlorideYield 94.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of the compound prepared in Example 9(54) (120 mg) and (1-methoxyisopropyl)oxyamine (31 mg) in dimethylformamide (1.6 ml) was added diisopropylethylamine (68 μl), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide.hydrochloride (56 mg) and 1-hydroxybenztriazole (40 mg). The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was added 1N hydrochloric acid (2 ml) and stirred for 15 minutes at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride and the obtained residue was dried over anhydrous sodium sulfate and concentrated. To a solution of the obtained residue in methanol was added 4N hydrogen chloride/ethyl acetate solution and concentrated. The obtained residue was washed with ethyl acetate to give the title compound (116 mg) having the following physical data.

Workup

  1. stirringstirred for 15 minutes at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with water, saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride
  4. dry with materialthe obtained residue was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. additionTo a solution of the obtained residue in methanol was added 4N hydrogen chloride/ethyl acetate solution
  7. concentrationconcentrated
  8. washThe obtained residue was washed with ethyl acetate

Sources & evidence

ORD record
ord-9f7506e9251347ddb37cbdfc8672b92d
Source dataset
uspto-grants-2006_05
Patent number
US07053090B2

Reaction notes

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