3,5-Dimethylisoxazole-4-carbonyl Chloride → (S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(3,5-dimethyl-isoxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid

HRID 391975

反応式

HRID 391975 の反応式
Cl.Cl.C[O:4][C:5](=[O:55])[C@@H:6]([NH:22][C:23]([C@@H:25]1[CH2:34][C:33]2[CH:32]=[C:31]3[O:35][CH2:36][C@H:37]([C:39]4[CH:44]=[CH:43][C:42]([O:45][CH2:46][C:47]5[CH:52]=[CH:51][C:50]([Cl:53])=[C:49]([Cl:54])[CH:48]=5)=[CH:41][CH:40]=4)[O:38][C:30]3=[CH:29][C:28]=2[CH2:27][NH:26]1)=[O:24])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[C:15]=2[CH3:21])=[CH:10][CH:9]=1.[CH3:56][C:57]1[C:61]([C:62](Cl)=[O:63])=[C:60]([CH3:65])[O:59][N:58]=1>CCOC(C)=O.C([O-])(O)=O.[Na+]>[Cl:54][C:49]1[CH:48]=[C:47]([CH:52]=[CH:51][C:50]=1[Cl:53])[CH2:46][O:45][C:42]1[CH:41]=[CH:40][C:39]([C@H:37]2[CH2:36][O:35][C:31]3=[CH:32][C:33]4[CH2:34][C@@H:25]([C:23]([NH:22][C@@H:6]([CH2:7][C:8]5[CH:13]=[CH:12][C:11]([C:14]6[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[C:15]=6[CH3:21])=[CH:10][CH:9]=5)[C:5]([OH:4])=[O:55])=[O:24])[N:26]([C:62]([C:61]5[C:57]([CH3:56])=[N:58][O:59][C:60]=5[CH3:65])=[O:63])[CH2:27][C:28]=4[CH:29]=[C:30]3[O:38]2)=[CH:44][CH:43]=1

参加物

5

反応物 2

HCID 27362653,5-Dimethylisoxazole-4-carbonyl ChlorideHCID 66719317(S)-2-({(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester dihydrochloride

生成物 1

HCID 58327116(S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(3,5-dimethyl-isoxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

(S)-2-({(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexa hydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester bis hydrochloride (25 mg) was dissolved in 1:1 EtOAc and saturated aqueous NaHCO3 and 3,5-dimethyl-isoxazole-4-carbonyl chloride (3 eq.) were added. After stirring at room temperature for 1 hour, the layers were separated and the organic layer was dried over Na2SO4 and evaporated. The residue was purified by over silica (hexanes to 8:2 hexanes-EtOAc to 6:4 hexanes-EtOAc to 6:4 hexanes-EtOAc+2% MeOH to DCM+3% MeOH). The resulting compound was hydrolyzed according to General Procedure B to give the title compound (16 mg). LCMS (m/z): 862.

後処理

  1. additionwere added
  2. customthe layers were separated
  3. dry with materialthe organic layer was dried over Na2SO4
  4. customevaporated
  5. customThe residue was purified by over silica (hexanes to 8:2 hexanes-EtOAc to 6:4 hexanes-EtOAc to 6:4 hexanes-EtOAc+2% MeOH to DCM+3% MeOH)

出典と根拠

ORDレコード
ord-8b0277e0ff6f42d29c8884f3cf930ceb
出典データセット
uspto-grants-2013_02
特許番号
US08383644B2

関連ノート

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