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Hydrochloric Acid → N-[5-Cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-piperazin-1-ylpiperidine-1-carboxamide

HRID 2408820
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HRID 2408820 반응식
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[O:23][CH3:24])(=[O:14])=[O:13])[C:7](=[O:25])[C:6]2([NH:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([N:44]2[CH2:49][CH2:48][N:47](C(OC(C)(C)C)=O)[CH2:46][CH2:45]2)[CH2:40][CH2:39]1)=[O:37])[C:26]1[C:27]([O:32][CH2:33][CH3:34])=[N:28][CH:29]=[CH:30][CH:31]=1)#[N:2].Cl.C(Cl)Cl.CO>CO.C(O)(C)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[O:23][CH3:24])(=[O:14])=[O:13])[C:7](=[O:25])[C:6]2([NH:35][C:36]([N:38]1[CH2:39][CH2:40][CH:41]([N:44]2[CH2:45][CH2:46][NH:47][CH2:48][CH2:49]2)[CH2:42][CH2:43]1)=[O:37])[C:26]1[C:27]([O:32][CH2:33][CH3:34])=[N:28][CH:29]=[CH:30][CH:31]=1)#[N:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 21226129Dichloromethane methanolHCID 67160388tert-Butyl 4-[1-({[5-cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]amino}carbonyl)piperidin-4-yl]piperazine-1-carboxylate

생성물 1

HCID 67159888N-[5-Cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-piperazin-1-ylpiperidine-1-carboxamide

시약·촉매·용매

2
HCID 887Methanol용매HCID 3776Isopropanol용매

실험 절차

55.3 mg (0.07 mmol) of tert-butyl 4-[1-({[5-cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3,-dihydro-1H-indol-3-yl]amino}carbonyl)piperidin-4-yl]piperazine-1-carboxylate were initially charged in 4 ml of methanol, and 1.0 ml of 5-6 M hydrochloric acid in isopropanol was added. The mixture was stirred at room temperature. The progress of the reaction was monitored by TLC (silica gel, CH2Cl2/MeOH 9:1). After complete conversion, the alcoholic solvent residues were removed, and the residue was taken up in dichloromethane and, using 1 N aqueous sodium hydroxide solution, adjusted by extraction to pH 9. The organic phase was separated from the aqueous phase, and the aqueous phase was reextracted with dichloromethane (2×). The combined organic phase was dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue was crystallized from diethyl ether. Alternatively, the residue can also be purified either by conventional column chromatography on a normal phase (NP-SiO2 cartridge, Chromabond) using dichloromethane/methanol as mobile phases or by preparative HPLC (RP, mobile phases acetonitrile/water, 0.01% TFA). After crystallization, 15.9 mg (0.023 mmol, 33%) of N-[5-cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-O-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-piperazin-1-ylpiperidine-1-carbox amide were isolated.

후처리

  1. customAfter complete conversion, the alcoholic solvent residues were removed
  2. extractionadjusted by extraction to pH 9
  3. customThe organic phase was separated from the aqueous phase
  4. dry with materialThe combined organic phase was dried over magnesium sulphate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was crystallized from diethyl ether
  7. customAlternatively, the residue can also be purified either by conventional column chromatography on a normal phase (NP-SiO2 cartridge, Chromabond)
  8. customAfter crystallization, 15.9 mg (0.023 mmol, 33%) of N-[5-cyano-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-O-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-piperazin-1-ylpiperidine-1-carbox amide
  9. customwere isolated

출처 및 근거

ORD 기록
ord-0f7d7d443fd64438b7b46bd3869f409f
출처 데이터셋
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08815868B2

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