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

Reaktionsgleichung

Reaktionsgleichung von HRID 391954
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

Komponenten

6

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-e6a17e5819274e059fe8518959c1d5d4
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08383644B2

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