Phosgene → 4,6-dimethoxy-2,3-dihydro-1H-indole-2,3-dione

HRID 526666Notes

Reaction equation

HRID 526666 reaction equation
NC1C=C(OC)C=C(OC)C=1C(N)=O.[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[NH:25][C:24](=O)[O:23][C:21](=[O:22])[C:20]2=[C:27]([O:29][CH3:30])[CH:28]=1.COC1C=C(N)C(=C(OC)C=1)C(O)=O.C(Cl)(Cl)=O.COC1C=C(C=C(OC)C=1)N.C(Cl)(=O)C(Cl)=O>>[CH3:30][O:29][C:27]1[CH:28]=[C:17]([O:16][CH3:15])[CH:18]=[C:19]2[C:20]=1[C:21](=[O:22])[C:24](=[O:23])[NH:25]2

Participants

7

Reactant 6

HCID 6371PhosgeneHCID 65578Oxalyl chlorideHCID 663013,5-DimethoxyanilineHCID 116010104,6-Dimethoxyisatoic anhydride2×HCID 116584562-Amino-4,6-dimethoxybenzoic acidHCID 203490162-Amino-4,6-dimethoxybenzamide

Product 1

HCID 115575224,6-dimethoxy-2,3-dihydro-1H-indole-2,3-dione

Procedure

2-Amino-4,6-dimethoxybenzamide has been prepared from 4,6-dimethoxyisatoic anhydride. The 4,6-dimethoxyisatoic anhydride was, in turn, prepared by a reaction of 4,6-dimethoxyanthranilic acid with phosgene (U.S. Pat. No. 4,191,840 and Org. Synth. 1947, 27, 45). A different route converts 3,5-dimethoxyaniline to its hydrochloride salt, after which the salt is reacted with oxalyl chloride to give 4,6-dimethoxyisatin. The isatin is converted to the target compound via an unstable carboxyl intermediate by reaction with sodium hydroxide and hydrogen peroxide followed by an EDCI/HOBt-mediated coupling to produce 2-amino-4,6-dimethoxybenzamide (WO 2008/92231).

Sources & evidence

ORD record
ord-ac513fd1a947446fb3ceb05b13b5b6e4
Source dataset
uspto-grants-2016_05
Patent number
US09346743B2

Reaction notes

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