1-Hydroxybenzotriazole → HCID 57920042、化合物

HRID 19268ノート

反応式

HRID 19268 の反応式
Cl[C:2]1[CH:3]=C(C=C[CH:25]=1)OC1CN([C@@H](CC2CCCCC2)C(O)=O)C(=O)C=1.Cl.[CH3:27]N(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.Cl.[OH:58][C@@H:59]([CH2:89]O)[CH2:60][N:61]1[CH:65]=[CH:64][C:63]([NH:66][C:67](=[O:88])[C@@H:68]([N:73]2[CH2:77][C:76]([O:78][C:79]3[CH:84]=[CH:83][CH:82]=[C:81]([Cl:85])[C:80]=3Cl)=[CH:75][C:74]2=[O:87])[CH2:69][CH:70]([CH3:72])[CH3:71])=[N:62]1>ClCCl.C(OCC)(=O)C>[Cl:85][C:81]1[CH:80]=[C:79]([CH:84]=[CH:83][CH:82]=1)[O:78][C:76]1[CH2:77][N:73]([C@@H:68]([CH2:69][CH:70]2[CH2:71][CH2:3][CH2:2][CH2:25][CH2:72]2)[C:67]([NH:66][C:63]2[CH:64]=[CH:65][N:61]([CH2:60][C:59]([OH:58])([CH3:27])[CH3:89])[N:62]=2)=[O:88])[C:74](=[O:87])[CH:75]=1

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66893063HCID 66893063、化合物HCID 66899094HMS5552 HCl

生成物 1

HCID 57920042HCID 57920042、化合物収率 29.9%

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)-2-[4-(3-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionic acid (200 mg, 0.6 mmol) in dichloromethane (10 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (115 mg, 0.6 mmol) and N,N-diisopropylethylamine (213 mg, 1.7 mmol) at room temperature, under nitrogen. After 15 min,, 1-hydroxybenzotriazole (0.092 g, 0.625 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 85 mg, 0.5 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)-2-[4-(3-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (0.075 g, 27%) as a white solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.84-1.11 (m, 2H), 1.16 (s, 3H), 1.19-1.35 (m, 3H), 1.27 (s, 3H), 1.60-1.98 (m, 8H), 3.39 (br. s., 1H), 3.95 (s, 2H), 4.09 (d, J=18.0 Hz, 1H), 4.28 (d, J=18.0 Hz, 1H), 4.89 (dd, J=9.2, 6.5 Hz, 1H), 5.03 (s, 1H), 6.69 (d, J=2.2 Hz, 1H), 7.09 (dd, J=8.2, 1.8 Hz, 1H), 7.21 (t, J=1.8 Hz, 1H), 7.27 (m, 1H), 7.30 (d, J=2.2 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 8.49 (br. 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-03a596bd57224a15902b31af6ebd2292
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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