Ammonium Chloride → 6-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)pyridazine-3-carboxamide

HRID 1714865Notes

Reaction equation

HRID 1714865 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[CH:24]=[CH:23][CH:22]=[CH:21][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[N:16][C:15]([C:18]([OH:20])=O)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1.C1C=CC2N(O)N=[N:33]C=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[F:1][C:2]([F:25])([F:26])[C:3]1[CH:24]=[CH:23][CH:22]=[CH:21][C:4]=1[O:5][CH:6]1[CH2:7][CH2:8][N:9]([C:12]2[N:17]=[N:16][C:15]([C:18]([NH2:33])=[O:20])=[CH:14][CH:13]=2)[CH2:10][CH2:11]1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 462254266-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)pyridazine-3-carboxylic acid

Product 1

HCID 462254256-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)pyridazine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 6-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine-3-carboxylic acid (250 mg, 0.7 mmol), HOBt (92 mg, 0.7 mmol), HATU (518 mg, 1.4 mmol) and ammonium chloride (74 mg, 1.4 mmol) in DMF (5 mL) was added N,N-diisopropylethylamine (592 μL, 3.4 mmol) at room temperature. The mixture was stirred at room temperature overnight, diluted with water and extracted with EtOAc. The organic extract was washed twice with 1N NaOH, brine, dried (Na2SO4) and concentrated. CombiFlash chromatography (10 g, 80-100% EtOAc in hexanes, 20 mL/min, 18 mL/fraction) gave the title compound as a white powder. 1H NMR (400 MHz, acetone-d6): δ 1.93-1.99 (m, 2H), 2.14-2.20 (m, 2H), 3.93-4.09 (m, 4H), 5.05 (s, 1H), 6.72 (s, 1H), 7.13 (t, 1H), 7.38 (m, 2H), 7.62-7.68 (m, 2H), 7.84 (s, 1H), 7.94 (d, 1H). MS (+ESI) m/z 367 (MH+).

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. washwas washed twice with 1N NaOH, brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-70f9858284274712a18b1aba533877ed
Source dataset
uspto-grants-2010_09
Patent number
US07799787B2

Reaction notes

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