5-chloro-N-((4S,6S)-4-(5-(5-chloropicolinamido)-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)picolinamide → N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide

HRID 930290Notes

Reaction equation

HRID 930290 reaction equation
ClC1C=CC(C([NH:10][C:11]2[O:12][C@H:13]([C:35]([F:38])([F:37])[F:36])[CH2:14][C@:15]([C:18]3[CH:23]=[C:22]([NH:24][C:25](=[O:33])[C:26]4[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][N:27]=4)[CH:21]=[CH:20][C:19]=3[F:34])([CH3:17])[N:16]=2)=O)=NC=1>N.CO>[NH2:10][C:11]1[O:12][C@H:13]([C:35]([F:36])([F:38])[F:37])[CH2:14][C@:15]([C:18]2[CH:23]=[C:22]([NH:24][C:25](=[O:33])[C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][N:27]=3)[CH:21]=[CH:20][C:19]=2[F:34])([CH3:17])[N:16]=1

Participants

3

Reactant 1

HCID 867321215-chloro-N-((4S,6S)-4-(5-(5-chloropicolinamido)-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)picolinamide

Product 1

HCID 71667461N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloropicolinamideYield 74.7%

Reagents, catalysts & solvents 1

HCID 21705897Ammonia methanolSolvent

Procedure

A solution of 5-chloro-N-((4S,6S)-4-(5-(5-chloropicolinamido)-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)picolinamide (4k 85.3 mg, 0.150 mmol) in 2 M NH3/MeOH (Aldrich; 4.0 mL) was heated to 50° C. for 16 h. The solution was concentrated and purified by flash chromatography on silica gel (Gradient: 20%→100% EtOAc/hexane) to give the title compound (48.2 mg, 0.112 mmol) as a white solid. MS m/z=431.0, [M+H]+. Calculated for C18H15ClF4N4O2: 430.8

Workup

  1. concentrationThe solution was concentrated
  2. custompurified by flash chromatography on silica gel (Gradient: 20%→100% EtOAc/hexane)

Sources & evidence

ORD record
ord-bfae3ee654f849ba8f9c1f3cf3a1964d
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

Loading…