Ammonia → N-(3-((4SR,6SR)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloro-3-methyl-2-pyridinecarboxamide

HRID 930294Notes

Reaction equation

HRID 930294 reaction equation
C([NH:9][C:10]1[O:11][C@H:12]([C:35]([F:38])([F:37])[F:36])[CH2:13][C@:14]([C:17]2[CH:18]=[C:19]([NH:24][C:25](=[O:34])[C:26]3[C:31]([CH3:32])=[CH:30][C:29]([Cl:33])=[CH:28][N:27]=3)[CH:20]=[CH:21][C:22]=2[F:23])([CH3:16])[N:15]=1)(=O)C1C=CC=CC=1.N>>[NH2:9][C:10]1[O:11][CH:12]([C:35]([F:38])([F:37])[F:36])[CH2:13][C:14]([C:17]2[CH:18]=[C:19]([NH:24][C:25]([C:26]3[C:31]([CH3:32])=[CH:30][C:29]([Cl:33])=[CH:28][N:27]=3)=[O:34])[CH:20]=[CH:21][C:22]=2[F:23])([CH3:16])[N:15]=1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 86732125N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloro-3-methylpicolinamide

Product 1

HCID 86732126N-(3-((4SR,6SR)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloro-3-methyl-2-pyridinecarboxamideYield 51.3%

Conditions

Temperature
80 °C

Procedure

A sealable vial was charged with N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloro-3-methylpicolinamide (rac 4n, 0.050 g, 0.091 mmol) and ammonia (2.0M solution in methanol; 3.0 ml, 6.00 mmol). The reaction mixture was heated to 80° C. for 17 hs. The reaction mixture was concentrated an the residue was diluted with a minimal amount of CH2Cl2. Purification by silica gel chromatography (gradient 0.0 to 5.0% 2 M ammonia in MeOH/CH2Cl2) afforded the title compound (0.0104 g, 0.023 mmol, 51.3% yield) as a white solid. MS m/z=445.0 [M+H]+. Calculated for C19H17ClF4N4O2: 444.098.

Workup

  1. concentrationThe reaction mixture was concentrated an the residue
  2. additionwas diluted with a minimal amount of CH2Cl2
  3. customPurification by silica gel chromatography (gradient 0.0 to 5.0% 2 M ammonia in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-3d69734dc13e4459bf0e39741f4f2ea3
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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