Veratric Acid → (S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(3,4-dimethoxy-benzoyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid

HRID 391963Notes

Reaction equation

HRID 391963 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([OH:8])=O.CCN=C=NCCCN(C)C.C[O:26][C:27](=[O:78])[C@@H:28]([NH:45][C:46]([C@@H:48]1[CH2:57][C:56]2[CH:55]=[C:54]3[O:58][CH2:59][C@H:60]([C:62]4[CH:67]=[CH:66][C:65]([O:68][CH2:69][C:70]5[CH:75]=[CH:74][C:73]([Cl:76])=[C:72]([Cl:77])[CH:71]=5)=[CH:64][CH:63]=4)[O:61][C:53]3=[CH:52][C:51]=2[CH2:50][NH:49]1)=[O:47])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][C:37]2[CH:42]=[CH:41][N:40]=[C:39]([CH3:43])[C:38]=2[CH3:44])=[CH:32][CH:31]=1>C(Cl)Cl>[Cl:77][C:72]1[CH:71]=[C:70]([CH:75]=[CH:74][C:73]=1[Cl:76])[CH2:69][O:68][C:65]1[CH:66]=[CH:67][C:62]([C@H:60]2[CH2:59][O:58][C:54]3=[CH:55][C:56]4[CH2:57][C@@H:48]([C:46]([NH:45][C@@H:28]([CH2:29][C:30]5[CH:35]=[CH:34][C:33]([O:36][C:37]6[CH:42]=[CH:41][N:40]=[C:39]([CH3:43])[C:38]=6[CH3:44])=[CH:32][CH:31]=5)[C:27]([OH:78])=[O:26])=[O:47])[N:49]([C:6](=[O:8])[C:5]5[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=5)[CH2:50][C:51]=4[CH:52]=[C:53]3[O:61]2)=[CH:63][CH:64]=1

Participants

5

Reactant 3

HCID 7121Veratric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 58327121(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-yloxy)-phenyl]-propionic acid methyl ester

Product 1

HCID 58327502(S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(3,4-dimethoxy-benzoyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3,4-Dimethoxybenzoic acid (1 eq.) was stirred in dry DCM with 0.5 eq EDCI at RT for 1 h. (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-yloxy)-phenyl]-propionic acid methyl ester in dry DCM (10 eq benzoic acid relative to amine) was added and the resulting mixture stirred 16 h, then directly purified by flash chromatography. The resulting compound was hydrolyzed according to General Procedure B to give the title compound (5 mg). LCMS (m/z) 919.

Workup

  1. additionwas added
  2. customdirectly purified by flash chromatography

Sources & evidence

ORD record
ord-c3c74fd8c2454052bc34998114730cdb
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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