1-Hydroxybenzotriazole → HCID 57920145, 화합물

HRID 19239노트

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HRID 19239 반응식
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=3[Cl:25])=[CH:14][C:13]2=[O:26])[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:28]N(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.Cl.[OH:59][C@@H:60]([CH2:90]O)[CH2:61][N:62]1[CH:66]=[CH:65][C:64]([NH:67]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:63]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]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=3[Cl:25])=[CH:14][C:13]2=[O:26])[C:9]([NH:67][C:64]2[CH:65]=[CH:66][N:62]([CH2:61][C:60]([OH:59])([CH3:90])[CH3:28])[N:63]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66895625(S)-3-cyclohexyl-2-[4-(2,5-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acidHCID 66899094HMS5552 HCl

생성물 1

HCID 57920145HCID 57920145, 화합물수율 30.3%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

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온도
23 °C

실험 절차

To a stirred solution of (S)-3-cyclohexyl-2-[4-(2,5-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (160 mg, 0.4 mmol) in dichloromethane (5 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (82 mg, 0.4 mmol) and N,N-diisopropylethylamine (210 mg, 1.6 mmol) at room temperature, under nitrogen. After 15 min,, 1-hydroxybenzotriazole (61 mg, 0.4 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 160 mg, 0.4 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-(2,5-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (0.065 g, 30%) as a brown sticky liquid: 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80-1.01 (m, 2H), 1.05 (s, 3H), 1.06 (s, 3H), 1.07-1.20 (m, 3H), 1.50-1.84 (m, 8H), 3.89 (s, 2H), 4.19 (d, J=18.1 Hz, 1H), 4.60 (d, J=18.1 Hz, 1H), 4.66 (s, 1H), 4.92 (dd, J=10.5, 5.1 Hz, 1H), 4.95 (s, 1H), 6.44 (d, J=2.0 Hz, 1H), 7.46 (dd, J=8.8, 2.4 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.75 (d, J=2.4 Hz, 1H), 10.76 (s, 1H).

후처리

  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

출처 및 근거

ORD 기록
ord-4a9da9628d394c2b99bd6b9c471ddf7d
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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