Raltegravir → 4-Fluorobenzylamine

HRID 1477509Notes

Reaction equation

[CH3:1][C:2]1[O:6][C:5]([C:7]([NH:9][C:10]([C:13]2[N:19](C)[C:17](=[O:18])[C:16]([OH:21])=[C:15]([C:22]([NH:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[O:23])[N:14]=2)([CH3:12])[CH3:11])=[O:8])=[N:4][N:3]=1.FC1C=CC(CN[C:40](C2N=C(C(NC(C3OC(C)=NN=3)=O)(C)C)NC(=O)C=2O)=[O:41])=CC=1>>[CH3:40][O:41][C:22]([C:15]1[N:14]=[C:13]([C:10]([NH:9][C:7]([C:5]2[O:6][C:2]([CH3:1])=[N:3][N:4]=2)=[O:8])([CH3:12])[CH3:11])[NH:19][C:17](=[O:18])[C:16]=1[OH:21])=[O:23].[F:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][NH2:24])=[CH:27][CH:28]=1

Participants

Reactant 2

HCID 54671008Raltegravir

HCID 1362364801446223-96-6

Product 2

HCID 673264-Fluorobenzylamine

HCID 136502909HCID 136502909, compound

Procedure

Among the advantages of the novel route of synthesis of raltegravir is the regioselective methylation of N-(4-fluorobenzyl)-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxamide (VI) obtained by amidation of methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate (Va) with p-fluorobenzyl amine. The methylation reaction provides regioselectivity of more than 99% as against methylation of oxygen at 6th position, thereby resulting in a higher yield of more than 90%. The yield for the methylation reaction is in the range of 88 to 90%.

Sources & evidence

ORD record: ord-f3d6f93e7d514351bf3c2e4523edfa9f
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403809B2

Reaction notes

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