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 708752Notes

Reaction equation

HRID 708752 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.Cl.C[O:27][C:28](=[O:79])[C@@H:29]([NH:46][C:47]([C@@H:49]1[CH2:58][C:57]2[CH:56]=[C:55]3[O:59][CH2:60][C@H:61]([C:63]4[CH:68]=[CH:67][C:66]([O:69][CH2:70][C:71]5[CH:76]=[CH:75][C:74]([Cl:77])=[C:73]([Cl:78])[CH:72]=5)=[CH:65][CH:64]=4)[O:62][C:54]3=[CH:53][C:52]=2[CH2:51][NH:50]1)=[O:48])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][C:38]2[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[C:39]=2[CH3:45])=[CH:33][CH:32]=1>C(Cl)Cl>[Cl:78][C:73]1[CH:72]=[C:71]([CH:76]=[CH:75][C:74]=1[Cl:77])[CH2:70][O:69][C:66]1[CH:67]=[CH:68][C:63]([C@H:61]2[CH2:60][O:59][C:55]3=[CH:56][C:57]4[CH2:58][C@@H:49]([C:47]([NH:46][C@@H:29]([CH2:30][C:31]5[CH:36]=[CH:35][C:34]([O:37][C:38]6[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[C:39]=6[CH3:45])=[CH:33][CH:32]=5)[C:28]([OH:79])=[O:27])=[O:48])[N:50]([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)[CH2:51][C:52]=4[CH:53]=[C:54]3[O:62]2)=[CH:64][CH:65]=1

Participants

5

Reactant 3

HCID 7121Veratric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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 EDCl 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-87ed151041914e81939cc5242a7d4663
Source dataset
uspto-grants-2015_11
Patent number
US09175003B2

Reaction notes

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