4-Iodobenzonitrile → (S)-8-[(S)-4-(4-cyano-phenyl)-1 methoxycarbonyl-but-3-ynylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester

HRID 391872Notes

Reaction equation

C(OC([N:8]1C(C(O)=O)C[C:15]2[CH:14]=[C:13]3OC[C@H](C4C=CC(OCC5C=CC(Cl)=C(Cl)C=5)=CC=4)O[C:12]3=[CH:11][C:10]=2[CH2:9]1)=O)(C)(C)C.[C:41]([O:45][C:46]([N:48]1[CH:57]([C:58](=[O:68])[NH:59][C@H:60]([C:64]([O:66][CH3:67])=[O:65])[CH2:61][C:62]#[CH:63])[CH2:56][C:55]2[CH:54]=[C:53]3[O:69][CH2:70][C@H:71]([C:73]4[CH:78]=[CH:77][C:76]([O:79][CH2:80][C:81]5[CH:86]=[CH:85][C:84]([Cl:87])=[C:83]([Cl:88])[CH:82]=5)=[CH:75][CH:74]=4)[O:72][C:52]3=[CH:51][C:50]=2[CH2:49]1)=[O:47])([CH3:44])([CH3:43])[CH3:42].IC1C=CC(C#N)=CC=1>>[C:41]([O:45][C:46]([N:48]1[CH:57]([C:58](=[O:68])[NH:59][C@H:60]([C:64]([O:66][CH3:67])=[O:65])[CH2:61][C:62]#[C:63][C:13]2[CH:12]=[CH:11][C:10]([C:9]#[N:8])=[CH:15][CH:14]=2)[CH2:56][C:55]2[CH:54]=[C:53]3[O:69][CH2:70][C@H:71]([C:73]4[CH:74]=[CH:75][C:76]([O:79][CH2:80][C:81]5[CH:86]=[CH:85][C:84]([Cl:87])=[C:83]([Cl:88])[CH:82]=5)=[CH:77][CH:78]=4)[O:72][C:52]3=[CH:51][C:50]=2[CH2:49]1)=[O:47])([CH3:44])([CH3:42])[CH3:43]

Participants

Reactant 3

HCID 764674-Iodobenzonitrile

HCID 66719307(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester

HCID 86654903(S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-8-((S)-1-methoxycarbonyl-but-3-ynylcarbamoyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester

Product 1

HCID 66719439(S)-8-[(S)-4-(4-cyano-phenyl)-1 methoxycarbonyl-but-3-ynylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl esterYield 40.3%

Procedure

(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester (59 mg) was coupled with (S)-propargyl-glycinemethylester hydrochloride (20 mg) according to General Procedure A. The resulting (S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-8-((S)-1-methoxycarbonyl-but-3-ynylcarbamoyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (26 mg) was reacted with 4-iodobenzonitrile (7 mg) according to General Procedure S to give (S)-8-[(S)-4-(4-cyano-phenyl)-1 methoxycarbonyl-but-3-ynylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (12 mg).

Sources & evidence

ORD record: ord-de458fa995bb4bd9b7cd6d196bd271d4
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383644B2

Reaction notes

Loading…