Diisopropylethylamine → 3-Amino-N'-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl)-5-(trifluoromethyl) picolinohydrazide

HRID 574216Notes

Reaction equation

HRID 574216 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4](O)=[O:5].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:44][C:45]1[C:46]([C:55]([NH:57][NH2:58])=[O:56])=[N:47][CH:48]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:50]=1>CN1C(=O)CCC1.O>[NH2:44][C:45]1[C:46]([C:55]([NH:57][NH:58][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[O:56])=[N:47][CH:48]=[C:49]([C:51]([F:53])([F:52])[F:54])[CH:50]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867296013-Amino-5-(trifluoromethyl)picolinohydrazide2×

Product 1

HCID 867296043-Amino-N'-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl)-5-(trifluoromethyl) picolinohydrazide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (324 mg, 2.049 mmol) in NMP (5 ml) was added HATU (935 mg, 2.458 mmol) and DIPEA (1.073 ml, 6.15 mmol). After stirring for 5 minutes 3-amino-5-(trifluoromethyl)picolinohydrazide (Intermediate I) (451 mg, 2.049 mmol) was added and stirring continued at RT for 1 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed with 1M HCl (100 ml), water (2×100 ml), brine and dried (phase separator) and concentrated in vacuo. Purification by chromatography on silica eluting with 0-30% EtOAc in iso-hexane afforded the title compound; 1H NMR 400 MHz, DMSO-d6: δ 10.3 (1H, s), 10.0 (1H, s), 8.0 (1H, s), 7.5 (1H, s), 7.1 (3H, s, overlap), 1.5 (3H, s). LC-MS Rt=0.98 min [M+H]+ 361.2 Method 2minLC_v003.

Workup

  1. additionwas added
  2. extractionextracted with EtOAc
  3. washThe combined organic extracts were washed with 1M HCl (100 ml), water (2×100 ml), brine
  4. customdried (phase separator)
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography on silica eluting with 0-30% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-6634c054b8c14c529bbd5830b8a15420
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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