Diisopropylethylamine → (R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoate

HRID 1782185노트

반응식

HRID 1782185 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19](=[O:22])[CH:20]=[CH2:21])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[Cl:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:26]=1[C:32]1[CH:36]=[C:35]([C:37]2[CH:42]=[C:41]([NH2:43])[CH:40]=[CH:39][N:38]=2)[O:34][N:33]=1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:19](=[O:22])[CH2:20][CH2:21][NH:43][C:41]1[CH:40]=[CH:39][N:38]=[C:37]([C:35]2[O:34][N:33]=[C:32]([C:26]3[C:25]([Cl:24])=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:31])[CH:36]=2)[CH:42]=1)[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:3])([CH3:4])[CH3:2]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 69053436HCID 69053436, 화합물HCID 86608878(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate

생성물 1

HCID 57588345(R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoate수율 43.7%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

반응 조건

온도
89 °C

실험 절차

(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate (0.94 g) and 2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-amine hydrochloride salt (0.40 g) were dissolved in acetonitrile (4 mL). Diisopropylethylamine (0.52 mL) was added and the mixture wad heated at 89° C. for 25 h. The mixture was cooled to room temperature, diluted with dichloromethane and washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography, on silica gel, eluting with 0.5:99.5 methanol:dichloromethane then 5:95 methanol:dichloromethane to yield (R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoate (316 mg) as a beige foam. 1H NMR (CDCl3): 8.25 (m, 1H), 7.40 (m, 2H), 7.30 (m, 1H), 7.17 (m, 1H), 6.98 (m, 1H), 6.47 (m, 1H), 5.20 (m, 1H), 5.00 (m, 1H), 4.22 (m, 1H), 3.59 (m, 2H), 2.90 (m, 2H), 2.32 (m, 2H), 2.10 (m, 1H), 1.83 (m, 1H), 1.45 ppm (s, 18H). MW=619 confirmed by LC-MS, tr=13.23 min (Method Y) MH+=617-621.

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by flash column chromatography, on silica gel
  7. washeluting with 0.5:99.5 methanol

출처 및 근거

ORD 기록
ord-ec3e3b0c7a8244189344af93d1df6ba5
출처 데이터셋
uspto-grants-2009_03
특허 번호
US07498353B2

반응 노트

불러오는 중…