1-Hydroxybenzotriazole → HCID 178473365、化合物

HRID 348085

反応式

HRID 348085 の反応式
[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]

参加物

9

反応物 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

生成物 1

HCID 178473365HCID 178473365、化合物

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回HCID 8471Triethylamine溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-825ee92b39b64acf8e1285551f69a761
出典データセット
uspto-grants-2007_02
特許番号
US07176207B2

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