1-Hydroxybenzotriazole → [2,4-Bis(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazin-1-yl]methanone

HRID 2411560노트

반응식

HRID 2411560 반응식
[O:1]=[S:2]1(=[O:23])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:15]=[C:14]([N:16]2[CH2:20][CH2:19][CH2:18][S:17]2(=[O:22])=[O:21])[CH:13]=[CH:12][C:8]=1[C:9](O)=[O:10].[CH:24]1([C:27]2[C:28]([N:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)=[N:29][CH:30]=[C:31]([CH3:33])[CH:32]=2)[CH2:26][CH2:25]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[O:23]=[S:2]1(=[O:1])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:15]=[C:14]([N:16]2[CH2:20][CH2:19][CH2:18][S:17]2(=[O:21])=[O:22])[CH:13]=[CH:12][C:8]=1[C:9]([N:37]1[CH2:38][CH2:39][N:34]([C:28]2[C:27]([CH:24]3[CH2:25][CH2:26]3)=[CH:32][C:31]([CH3:33])=[CH:30][N:29]=2)[CH2:35][CH2:36]1)=[O:10]

참가 물질

7

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 584846211-(3-Cyclopropyl-5-methylpyridin-2-yl)piperazineHCID 712522932,4-Bis(1,1-dioxo-1lambda6-isothiazolidin-2-yl)benzoic acid

생성물 1

HCID 71252172[2,4-Bis(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazin-1-yl]methanone

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

2,4-Bis(1,1-dioxo-1λ6-isothiazolidin-2-yl)benzoic acid (200 mg) described in Preparation Example 34, 1-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine (121 mg) described in Preparation Example 86, and 1-hydroxybenzotriazole 1 hydrate (79 mg) were dissolved in N,N-dimethylformamide (3 mL), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (112 mg) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (ethyl acetate:hexane) to give [2,4-bis(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazin-1-yl]methanone. The obtained [2,4-bis(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazin-1-yl]methanone (240 mg) was dissolved in ethyl acetate, 4N hydrogen chloride/ethyl acetate (0.11 mL) was added, and the precipitate was collected by filtration to give the title compound (104 mg).

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. customthe solvent was evaporated
  4. customThe obtained residue was purified by column chromatography (ethyl acetate:hexane)

출처 및 근거

ORD 기록
ord-a824ebc8d4b64a4b916e72b656f19bb5
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08816079B2

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