4-Methylmorpholine → 3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

HRID 887834Notes

Reaction equation

HRID 887834 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.Cl.[NH2:17][CH2:18][C:19]([CH3:25])([OH:24])[C:20]([F:23])([F:22])[F:21].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C.C(Cl)(Cl)Cl>[F:21][C:20]([F:23])([F:22])[C:19]([OH:24])([CH3:25])[CH2:18][NH:17][C:13]([C:3]1[C:2]([NH2:1])=[CH:7][C:6]([C:8]([F:9])([F:10])[F:11])=[C:5]([Br:12])[N:4]=1)=[O:15]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 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 acid2×HCID 717573513-Amino-1,1,1-trifluoro-2-methylpropan-2-ol hydrochloride

Product 1

HCID 534723853-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate A) (397 mg, 1.392 mmol), 3-amino-1,1,1-trifluoro-2-methyl-propan-2-ol hydrochloride (250 mg, 1.392 mmol) and HATU (529 mg, 1.392 mmol) were dissolved in DMF (10 ml) and stirred at RT for 2 min. 4-Methylmorpholine (0.413 ml, 4.18 mmol) was added and stirring continued at RT for 3 h. The reaction mixture was poured onto ice/water (100 ml) and extracted with EtOAc (250 ml). The organic extract was washed with sat NH4Cl solution (˜50 ml), dried over MgSO4 and concentrated in vacuo to give a pale brown oil. The oil was dissolved in CHCl3 (˜3 ml) and loaded onto a 24 g ISCO (silica) column eluting with iso-hexane:EtOAc to afford the title product; LC-MS Rt=1.46 mins; [M+H]+410.1, Method 2minLC_v002. 1H NMR (400 MHz, DMSO-d6) δ 8.30 (NH, t), 7.72 (1H, s), 7.29 (NH2, bs), 6.28 (OH, s), 3.68 (1H, dd), 3.47 (1H, dd), 1.24 (3H, s). 19F NMR (400 MHz, DMSO-d6) δ −62.71 (CF3, s), −80.48 (C3, s).

Workup

  1. stirringstirring
  2. waitcontinued at RT for 3 h
  3. additionThe reaction mixture was poured onto ice/water (100 ml)
  4. extractionextracted with EtOAc (250 ml)
  5. extractionThe organic extract
  6. washwas washed with sat NH4Cl solution (˜50 ml)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customto give a pale brown oil
  10. washeluting with iso-hexane

Sources & evidence

ORD record
ord-95760901983e4aabb3dd813bb8527d81
Source dataset
uspto-grants-2012_08
Patent number
US08247436B2

Reaction notes

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