3-Chloro-5-cyanopyridine-2-carboxylic acid → 3-chloro-5-cyano-pyridine-2-carboxylic acid [3-((R)-2-amino-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide

HRID 1941805Notes

Reaction equation

HRID 1941805 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@:8]2([CH3:19])[C:13]([F:15])([F:14])[C:12]([CH3:17])([CH3:16])[O:11][C:10]([NH2:18])=[N:9]2)[CH:7]=1.[Cl:21][C:22]1[C:23]([C:30](O)=[O:31])=[N:24][CH:25]=[C:26]([C:28]#[N:29])[CH:27]=1>>[NH2:18][C:10]1[O:11][C:12]([CH3:16])([CH3:17])[C:13]([F:14])([F:15])[C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:30]([C:23]3[C:22]([Cl:21])=[CH:27][C:26]([C:28]#[N:29])=[CH:25][N:24]=3)=[O:31])[CH:3]=[CH:4][C:5]=2[F:20])([CH3:19])[N:9]=1

Participants

3

Reactant 2

HCID 508531763-Chloro-5-cyanopyridine-2-carboxylic acidHCID 58304251(R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Product 1

HCID 532420313-chloro-5-cyano-pyridine-2-carboxylic acid [3-((R)-2-amino-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide

Procedure

The condensation of (R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate XI-2) and 3-chloro-5-cyano-pyridine-2-carboxylic acid following procedure I yielded the 3-chloro-5-cyano-pyridine-2-carboxylic acid [3-((R)-2-amino-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide which, after treatment with hydrochloric acid in dioxane (4N), evaporation and trituration with diethylether, gave the title compound as a white solid. MS (ISP): m/z=452.1 [M+H]+.

Sources & evidence

ORD record
ord-5b1611585646406a8d8eb20f7071d762
Source dataset
uspto-grants-2013_03
Patent number
US08389513B2

Reaction notes

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