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 1181584노트

반응식

HRID 1181584 반응식
[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]

참가 물질

9

반응물 6

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

생성물 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.hydrochloride수율 94.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a suspension of the compound prepared in Example 75(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.

후처리

  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

출처 및 근거

ORD 기록
ord-03b170e314004e999b55d01aad2f8403
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07285552B2

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