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

HRID 1782185ノート

反応式

HRID 1782185 の反応式
[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]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 69053436HCID 69053436、化合物HCID 86608878(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate

生成物 1

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

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
89 °C

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-ec3e3b0c7a8244189344af93d1df6ba5
出典データセット
uspto-grants-2009_03
特許番号
US07498353B2

反応ノート

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