Phenylacetic Acid → 3-Amino-6-bromo-N'-(2-phenylacetyl)-5-(trifluoromethyl)pyrazine-2-carbohydrazide

HRID 574202Notes

Reaction equation

HRID 574202 reaction equation
[C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:11][C:12]1[C:13]([C:23]([NH:25][NH2:26])=[O:24])=[N:14][C:15]([Br:22])=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN1C(=O)CCC1.CCOC(C)=O>[NH2:11][C:12]1[C:13]([C:23]([NH:25][NH:26][C:8](=[O:10])[CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:24])=[N:14][C:15]([Br:22])=[C:16]([C:18]([F:20])([F:21])[F:19])[N:17]=1

Participants

7

Reactant 4

HCID 999Phenylacetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867295903-Amino-6-bromo-5-(trifluoromethyl)pyrazine-2-carbohydrazide

Product 1

HCID 867295913-Amino-6-bromo-N'-(2-phenylacetyl)-5-(trifluoromethyl)pyrazine-2-carbohydrazide

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a stirred solution of phenyl acetic acid (95.0 mg, 0.698 mmol) in NMP (6 ml) was added a solution 3-amino-6-bromo-5-(trifluoromethyl)pyrazine-2-carbohydrazide (step 1) (250 mg, 0.837 mmol) in NMP (6 ml) followed by DIPEA (609 ul, 3.49 mmol). The resulting mixture was treated with HATU (398 mg, 1.047 mmol) portionwise and stirred at RT for 90 min. The mixture was added to EtOAc (50 ml) and washed with 0.1M NaOH (50 ml). The aqueous layer was back extracted with EtOAc (50 ml). The combined organic portions were washed with water (50 ml), brine (50 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by chromatography on silica eluting with 1:1 EtOAc/iso-hexane to afford the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.65 (1H, s), 10.29 (1H, s), 8.02 (2H, s), 7.30 (5H, m), 3.52 (2H, s). 19F NMR (400 MHz, DMSO-d6) δ-66 (s, CF3).

Workup

  1. washwashed with 0.1M NaOH (50 ml)
  2. extractionThe aqueous layer was back extracted with EtOAc (50 ml)
  3. washThe combined organic portions were washed with water (50 ml), brine (50 ml)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography on silica eluting with 1:1 EtOAc/iso-hexane

Sources & evidence

ORD record
ord-0453d4c51ba2455c88791f6339d4fb24
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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