Triphenylphosphine → (S)-2-({(3S,8S)-7-Benzoyl-3-[4-(3,3-dimethyl-butoxy)-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

HRID 391954

反応式

HRID 391954 の反応式
C[O:2][C:3](=[O:52])[C@@H:4]([NH:20][C:21]([C@@H:23]1[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40](O)=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25][N:24]1[C:44](=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=2[CH3:19])=[CH:8][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:72][C:73]([CH3:78])([CH3:77])[CH2:74][CH2:75][OH:76].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[C:44]([N:24]1[C@H:23]([C:21]([NH:20][C@@H:4]([CH2:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=3[CH3:19])=[CH:8][CH:7]=2)[C:3]([OH:52])=[O:2])=[O:22])[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40]([O:76][CH2:75][CH2:74][C:73]([CH3:78])([CH3:77])[CH3:72])=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25]1)(=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 122333,3-Dimethyl-1-butanolHCID 5363146Diisopropyl azodicarboxylateHCID 58327345(S)-2-{[(3S,8S)-7-Benzoyl-3-(4-hydroxy-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

生成物 1

HCID 58327144(S)-2-({(3S,8S)-7-Benzoyl-3-[4-(3,3-dimethyl-butoxy)-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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(S)-2-{[(3S,8S)-7-Benzoyl-3-(4-hydroxy-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 (18 mg) was dissolved in DCM, triphenyl phosphine (5.9 eq.). 3,3-Dimethyl-butan-1-ol (excess) added and mixture cooled on ice. DIAD (5.1 eq.) was added and the reaction mixture stirred on ice for 10 minutes and rt for 16 hours. The reaction mixture was directly purified over silica (DCM-EtOAc 8:2 to DCM-EtOAc 6:4). The resulting residue was hydrolyzed according to General Procedure B and purified over silica (DCM to DCM+1% MeOH to DCM+7% MeOH) to give the title compound (11 mg). LCMS (m/z): 769.

後処理

  1. temperaturemixture cooled on ice
  2. customThe reaction mixture was directly purified over silica (DCM-EtOAc 8:2 to DCM-EtOAc 6:4)
  3. custompurified over silica (DCM to DCM+1% MeOH to DCM+7% MeOH)

出典と根拠

ORDレコード
ord-e6a17e5819274e059fe8518959c1d5d4
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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