(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 → (S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2,5-dimethyl-oxazole-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 391939Notes

Reaction equation

Cl.Cl.COC(=O)[C@@H](NC([C@@H]1CC2C=C3OC[C@H](C4C=CC(OCC5C=CC(Cl)=C(Cl)C=5)=CC=4)OC3=CC=2CN1)=O)CC1C=CC(C2C=CN=C(C)C=2C)=CC=1.C[O:57][C:58](=[O:117])[C@@H:59]([NH:75][C:76]([C@@H:78]1[CH2:87][C:86]2[CH:85]=[C:84]3[O:88][CH2:89][C@H:90]([C:92]4[CH:97]=[CH:96][C:95]([O:98][CH2:99][C:100]5[CH:105]=[CH:104][C:103]([Cl:106])=[C:102]([Cl:107])[CH:101]=5)=[CH:94][CH:93]=4)[O:91][C:83]3=[CH:82][C:81]=2[CH2:80][N:79]1[C:108]([C:110]1[N:111]=[C:112]([CH3:116])[O:113][C:114]=1[CH3:115])=[O:109])=[O:77])[CH2:60][C:61]1[CH:66]=[CH:65][C:64]([C:67]2[CH:72]=[CH:71][N:70]=[C:69]([CH3:73])[C:68]=2[CH3:74])=[CH:63][CH:62]=1>>[Cl:107][C:102]1[CH:101]=[C:100]([CH:105]=[CH:104][C:103]=1[Cl:106])[CH2:99][O:98][C:95]1[CH:96]=[CH:97][C:92]([C@H:90]2[CH2:89][O:88][C:84]3=[CH:85][C:86]4[CH2:87][C@@H:78]([C:76]([NH:75][C@@H:59]([CH2:60][C:61]5[CH:66]=[CH:65][C:64]([C:67]6[CH:72]=[CH:71][N:70]=[C:69]([CH3:73])[C:68]=6[CH3:74])=[CH:63][CH:62]=5)[C:58]([OH:117])=[O:57])=[O:77])[N:79]([C:108]([C:110]5[N:111]=[C:112]([CH3:116])[O:113][C:114]=5[CH3:115])=[O:109])[CH2:80][C:81]=4[CH:82]=[C:83]3[O:91]2)=[CH:93][CH:94]=1

Participants

Reactant 2

HCID 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

HCID 66719612(S)-2-{[(3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-7-(2,5-dimethyl-oxazole-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 methyl ester

Product 1

HCID 58327378(S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2,5-dimethyl-oxazole-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

Procedure

(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 bis hydrochloride (25 mg) was converted to (S)-2-{[(3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-7-(2,5-dimethyl-oxazole-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 methyl ester according to General Procedure F. The resulting compound was hydrolyzed according to General Procedure B to give the title compound (15 mg). LCMS (m/z): 862.

Sources & evidence

ORD record: ord-a56d0907c20d43c793f0ff5728ef58a7
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383644B2

Reaction notes

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