Ethyl Acetate → (R)-Benzyl 2-(2-(3-amino-6-bromo-5-(trifluoromethyl)picolinoyl)hydrazinyl)-2-oxo-1-phenylethylcarbamate

HRID 574215Notes

Reaction equation

HRID 574215 reaction equation
[NH2:1][C:2]1[C:3]([C:13]([OH:15])=O)=[N:4][C:5]([Br:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[NH:16]([C:18](=[O:37])[C@H:19]([NH:26][C:27](=[O:36])[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[NH2:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCOC(C)=O>CN1C(=O)CCC1>[NH2:1][C:2]1[C:3]([C:13]([NH:17][NH:16][C:18](=[O:37])[C@H:19]([NH:26][C:27](=[O:36])[O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:15])=[N:4][C:5]([Br:12])=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584423503-Amino-6-bromo-5-(trifluoromethyl)picolinic acidHCID 86729603(R)-benzyl 2-hydrazinyl-2-oxo-1-phenylethylcarbamate

Product 1

HCID 86729602(R)-Benzyl 2-(2-(3-amino-6-bromo-5-(trifluoromethyl)picolinoyl)hydrazinyl)-2-oxo-1-phenylethylcarbamate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A suspension of 3-amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (Int. A) (200 mg, 0.702 mmol) in NMP (6 ml) was treated with (R)-benzyl 2-hydrazinyl-2-oxo-1-phenylethylcarbamate (Int. JR) (231 mg, 0.772 mg) followed by portionwise addition of HATU (293 mg, 0.772 mmol). After stirring at RT for 45 minutes, the reaction mixture was added to EtOAc (50 ml) and washed with 0.1 M NaOH (50 ml). The aqueous layer was back extracted with EtOAc (25 ml). The combined organic portions were washed with water (75 ml), brine (50 ml), dried (MgSO4) and concentrated in vacuo. The crude product was loaded in MeOH onto a pre-wetted (MeOH) Isolute® PE-AX (anion exchange) cartridge. The cartridge was eluted with MeOH (70 ml) and the filtrate was concentrated in vacuo to give a yellow solid which was placed under high vacuum to give the title compound as a yellow solid;

Workup

  1. washwashed with 0.1 M NaOH (50 ml)
  2. extractionThe aqueous layer was back extracted with EtOAc (25 ml)
  3. washThe combined organic portions were washed with water (75 ml), brine (50 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. washThe cartridge was eluted with MeOH (70 ml)
  7. concentrationthe filtrate was concentrated in vacuo
  8. customto give a yellow solid which

Sources & evidence

ORD record
ord-9bc85a9c1148458d8dcebaf7a29a4b75
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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