1-Hydroxybenzotriazole → (S)-3-cyclohexyl-2-[4-(2,3-dimethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide

HRID 19229ノート

反応式

HRID 19229 の反応式
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=3[O:26][CH3:27])=[CH:14][C:13]2=[O:28])[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:30]N(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.Cl.[OH:61][C@@H:62]([CH2:92]O)[CH2:63][N:64]1[CH:68]=[CH:67][C:66]([NH:69]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:65]1>ClCCl.C(OCC)(=O)C>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=3[O:26][CH3:27])=[CH:14][C:13]2=[O:28])[C:9]([NH:69][C:66]2[CH:67]=[CH:68][N:64]([CH2:63][C:62]([OH:61])([CH3:92])[CH3:30])[N:65]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66899094HMS5552 HClHCID 66899762HCID 66899762、化合物

生成物 1

HCID 57920099(S)-3-cyclohexyl-2-[4-(2,3-dimethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide収率 42%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
23 °C

実験手順

To a stirred solution of (S)-3-cyclohexyl-2-[4-(2,3-dimethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (150 mg, 0.39 mmol) in dichloromethane (8 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (225 mg, 1.2 mol) and N,N-diisopropylethylamine (254 mg, 2.0 mol) at room temperature, under nitrogen. After 15 min, 1-hydroxybenzotriazole (180 mg, 1.2 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 60 mg, 0.39 mmol) were added to the reaction mixture. The reaction mixture was then stirred at 23° C. for 48 h. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous ammonium chloride solution followed by a saturated aqueous sodium bicarbonate solution. The organic layer was then washed with a saturated aqueous sodium chloride solution, separated, dried over sodium sulfate and concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (silica gel (100-200 mesh)) which afforded (S)-3-cyclohexyl-2-[4-(2,3-dimethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (85 mg, 42%) as a light brown sticky solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.82-1.09 (m, 2H), 1.15 (br. s., 3H), 1.16 (br. s., 3H), 1.18-1.32 (m, 3H), 1.60-1.96 (m, 8H), 3.68 (s, 1H), 3.84 (s, 3H), 3.90 (s, 3H), 3.94 (s, 2H), 4.10 (d, J=17.9 Hz, 1H), 4.26 (d, J=17.9 Hz, 1H), 4.89 (dd, J=8.8, 6.8 Hz, 1H), 4.97 (s, 1H), 6.69 (d, J=2.1 Hz, 1H), 6.78 (d, J=8.3 Hz, 1H), 6.84 (d, J=8.3 Hz, 1H), 7.05 (t, J=8.3 Hz, 1H), 7.30 (d, J=2.1 Hz, 1H), 8.64 (s, 1H).

後処理

  1. customat room temperature
  2. washwashed with a saturated aqueous ammonium chloride solution
  3. washThe organic layer was then washed with a saturated aqueous sodium chloride solution
  4. customseparated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford the crude product, which
  8. customwas purified by flash column chromatography (silica gel (100-200 mesh)) which

出典と根拠

ORDレコード
ord-5dbab17518104ce1a920cccf487dc790
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

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