Ammonium Chloride → 3-Tert-butyl-isoxazole-5-carboxylic acid [3-amino-4-chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide

HRID 1481533Notes

Reaction equation

HRID 1481533 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:17])([F:16])[F:15])[N:5]=[C:4]([NH:18][C:19]([C:21]2[O:25][N:24]=[C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:22]=2)=[O:20])[C:3]=1[N+:30]([O-])=O.[Cl-].[NH4+]>CCO.O.[Fe]>[NH2:30][C:3]1[C:4]([NH:18][C:19]([C:21]2[O:25][N:24]=[C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:22]=2)=[O:20])=[N:5][C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:15])([F:16])[F:17])=[CH:7][C:2]=1[Cl:1]

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 674109013-Tert-butyl-isoxazole-5-carboxylic acid [4-chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide

Product 1

HCID 674111003-Tert-butyl-isoxazole-5-carboxylic acid [3-amino-4-chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-tert-butyl-isoxazole-5-carboxylic acid [4-chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide (40.7 mg, 0.0868 mmol, prepared as described in STEP A above) in EtOH (5 mL) and water (2.5 mL) was treated with ammonium chloride (46.4 mg, 0.868 mmol) and iron powder (24.2 mg, 0.434 mmol), and the mixture was stirred at 50° C. for 3 h. The cooled mixture was concentrated in vacuo and partitioned between EtOAc (25 mL) and water (20 mL). The aqueous layer was extracted with EtOAc (20 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 12-g SEPRA Si 50 SPE column (Flow rate=20 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:3 over 40 min) to yield 3-tert-butyl-isoxazole-5-carboxylic acid [3-amino-4-chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calculated for C21H18N4O2ClF3: 439.1 (M+H). Measured: 439.1.

Workup

  1. concentrationThe cooled mixture was concentrated in vacuo
  2. custompartitioned between EtOAc (25 mL) and water (20 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 12-g SEPRA Si 50 SPE column (Flow rate=20 mL/min
  7. waitEluent=EtOAc-hexanes, 1:99 for 10 min

Sources & evidence

ORD record
ord-5cdae59d01014aaa8619c9556036f9e1
Source dataset
uspto-grants-2016_08
Patent number
US09409915B2

Reaction notes

Loading…