Water → 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [5-amino-6-methyl-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide

HRID 570254Notes

Reaction equation

HRID 570254 reaction equation
[CH3:1][C:2]1[N: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[N:22]([CH3:30])[N:23]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:25]=2)=[O:20])[C:3]=1[N+:31]([O-])=O.O.[Cl-].[NH4+]>C(O)C.[Fe]>[NH2:31][C:3]1[C:4]([NH:18][C:19]([C:21]2[N:22]([CH3:30])[N:23]=[C:24]([C:26]([CH3:28])([CH3:27])[CH3:29])[CH:25]=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:17])[F:16])=[N:7][C:2]=1[CH3:1]

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 674115755-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide

Product 1

HCID 674110325-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [5-amino-6-methyl-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide (226 mg, 0.490 mmol, prepared as described in the previous step) in ethanol (10 mL) and water (5 mL) was treated with ammonium chloride (262 mg, 4.90 mmol) and iron powder (137 mg, 2.45 mmol), and the mixture was heated to 50° C. for 4 h. Ethanol was removed in vacuo, and the resulting residue was diluted with water (20 mL) and extracted twice with EtOAc (30 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system: Flow rate=20 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 10 min, then 1:99 to 1:4 v/v over 40 min) to yield 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [5-amino-6-methyl-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide as an off-white solid. Mass Spectrum (LCMS, APCI pos.): Calculated for C21H23F3N6O: 433.2 (M+H); Measured: 433.2.

Workup

  1. customEthanol was removed in vacuo
  2. additionthe resulting residue was diluted with water (20 mL)
  3. extractionextracted twice with EtOAc (30 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system

Sources & evidence

ORD record
ord-d17062de54e248c3933bb0e8430172ad
Source dataset
uspto-grants-2015_05
Patent number
US09023846B2

Reaction notes

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