1-Hydroxybenzotriazole → HCID 178473365, 화합물

HRID 348085

반응식

HRID 348085 반응식
[C:1]([C:4]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1)([OH:3])=O.[CH2:16]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]([CH:29]([NH2:36])[CH2:30][C:31]2[N:32]=[CH:33][NH:34][CH:35]=2)=[O:28])[CH2:23][CH2:22]1)=[O:20])[CH3:17].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C1COCC1.C(Cl)Cl.CO.C(N(CC)CC)C>[CH2:16]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]([CH:29]([NH:36][C:1]([C:4]2[CH:13]=[C:12]([O:14][CH3:15])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)=[O:3])[CH2:30][C:31]2[N:32]=[CH:33][NH:34][CH:35]=2)=[O:28])[CH2:23][CH2:22]1)=[O:20])[CH3:17]

참가 물질

9

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 5945964-Methoxy-2-quinolinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1784734004-Ethoxycarbonyl-1-(1-amino-2-(imidazol-4-yl)ethyl)carbonylpiperazine

생성물 1

HCID 178473365HCID 178473365, 화합물

시약·촉매·용매 4

HCID 887Methanol용매HCID 6344Dichloromethane용매2회HCID 8028Tetrahydrofuran용매2회HCID 8471Triethylamine용매2회

실험 절차

To a solution of N-t-butoxycarbonylhistidine (2 g, 7.05 mmol) in THF (30 mL) was added 1-ethoxycarbonylpiperazine (1.36 mL, 1.3 eq.), EDCI (1.65 g, 1.2 eq. ), HOBt (1.2 g, 1.1 eq.) and the reaction mixture was stirred overnight. The reaction mixture was evaporated in vacuo to afford a crude product, which was dissolved in ethyl acetate, washed with saturated NaHCO3, 1M NaHSO4 and brine. The organic layer was evaporated. Flash column chromatography with 2%–6% MeOH in CH2Cl2 afforded 4-ethoxycarbonyl-1-(1-(t-butoxycarbonyl)amino-2-(imidazol-4-yl)ethyl)carbonylpiperazine (820 mg). 4-Ethoxycarbonyl-1-(1-(t-butoxycarbonyl)amino-2-(imidazol-4-yl)ethyl)carbonylpiperazine (200 mg, 0.5 mmol) was treated with trifluoroacetic acid/methylene chloride (1:1, 2.0 mL) with stirring at ambient temperture for 1 hour. Evaporation gave 4-ethoxycarbonyl-1-(1-amino-2-(imidazol-4-yl)ethyl)carbonylpiperazine, which was treated with methylene chloride and triethylamine (0.5 mL), and the solvents evaporated to again afford 4-ethoxycarbonyl-1-(1-amino-2-(imidazol-4-yl)ethyl)carbonylpiperazine. To a solution of 2-carboxy-4-methoxyquinoline (124 mg, 0.61 mmol) in THF (4 mL) was added a mixture of 4-ethoxycarbonyl-1-(1-amino-2-(imidazol-4-yl)ethyl)carbonylpiperazine, THF (2 mL), and triethylamine (0.1 mL), followed by addition of EDCl (136 mg, 1.4 eq.), HOBt (98 mg, 1.4 eq.). The resulting mixture was stirred overnight. The crude product (245 mg, foam) was isolated from the reaction mixture by the same methods employed above. Flash column chromatography with 25%–6% MeOH in methylene chloride afforded 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-2-(imidazol-4-yl)ethyl]aminocarbonyl-4-methoxyquinoline; NMR (CDCl3) 1.25 (t, 3), 3.10–3.30 (m, 2), 3.20–3.65 (m, 9), 4.10 (m, 5), 5.40 (m, 1), 6.90 (s, 1), 7.55–7.60 (m, 3), 7.70 (t, 1), 8.02 (d, 1), 8.20 (d, 1), 9.0 (d, 1) ppm.

후처리

  1. customthe solvents evaporated to again afford 4-ethoxycarbonyl-1-(1-amino-2-(imidazol-4-yl)ethyl)carbonylpiperazine
  2. customThe crude product (245 mg, foam) was isolated from the reaction mixture by the same methods

출처 및 근거

ORD 기록
ord-825ee92b39b64acf8e1285551f69a761
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07176207B2

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