Thionyl Chloride → 2-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide

HRID 1840626Notes

Reaction equation

HRID 1840626 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.ClC1N=CC=CC=1C(Cl)=O.[Cl:25][C:26]1[C:31]([NH2:32])=[C:30]([CH3:33])[CH:29]=[CH:28][N:27]=1>>[Cl:1][C:2]1[C:3]([C:4]([NH:32][C:31]2[C:26]([Cl:25])=[N:27][CH:28]=[CH:29][C:30]=2[CH3:33])=[O:6])=[CH:7][CH:8]=[CH:9][N:10]=1

Participants

5

Reactant 4

HCID 24386Thionyl ChlorideHCID 762582-Chloronicotinic acidHCID 27563873-Amino-2-chloro-4-methylpyridineHCID 27745412-Chloronicotinoyl chloride

Product 1

HCID 104238682-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide

Procedure

In the method of Hargrave et al., 2-chloronicotinoyl chloride is formed by reacting 2-chloronicotinic acid with thionyl chloride. Next, as shown in Scheme 1, the reaction of 2-chloronicotinoyl chloride with 2-chloro-4-methyl-3-pyridinamine produces 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide. This is reacted with cyclopropylamine to give N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide. The final step is the cyclization to produce nevirapine, which occurs on treatment of the final intermediate with sodium hydride.

Sources & evidence

ORD record
ord-473da94e5ed2490d8eb03aae71a8293b
Source dataset
uspto-grants-2004_01
Patent number
US06680383B1

Reaction notes

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