Diisopropylethylamine → N-(2-Cyclopropyl-2-hydroxyethyl)-6-{4-[2-(trifluoromethy)phenoxy]piperidin-1-yl}pyridazine-3-carboxamide

HRID 1714867Notes

Reaction equation

HRID 1714867 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](O)=[O:19])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1.[NH2:27][CH2:28][CH:29]([CH:31]1[CH2:33][CH2:32]1)[OH:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[CH:31]1([CH:29]([OH:30])[CH2:28][NH:27][C:18]([C:15]2[N:16]=[N:17][C:12]([N:9]3[CH2:10][CH2:11][CH:6]([O:5][C:4]4[CH:21]=[CH:22][CH:23]=[CH:24][C:3]=4[C:2]([F:26])([F:1])[F:25])[CH2:7][CH2:8]3)=[CH:13][CH:14]=2)=[O:19])[CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 148520982-Amino-1-cyclopropylethan-1-olHCID 462254266-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)pyridazine-3-carboxylic acid

Product 1

HCID 57647121N-(2-Cyclopropyl-2-hydroxyethyl)-6-{4-[2-(trifluoromethy)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 (120 mg, 0.3 mmol), 2-amino-1-cyclopropylethanol (57 mg, 0.56 mmol) and HATU (249 mg, 0.65 mmol) in DMF (4 mL) was added N,N-diisopropylethylamine (285 μL, 3.4 mmol) at room temperature. The mixture was stirred at room temperature for 4 h, diluted with water and extracted with EtOAc. The EtOAc extract was washed with water, diluted twice with brine, dried (Na2SO4) and concentrated. CombiFlash chromatography (10 g, 90-100% EtOAc in hexanes in 20 min, 20 mL/min, 18 mL/fraction) gave the title compound as a light brown foam. 1H NMR (400 MHz, acetone-d6): δ 0.30-0.52 (m, 4H), 0.93-1.01 (m, 1H), 1.92-2.00 (m, 2H), 2.14-2.24 (m, 2H), 3.22-3.28 (m, 1H), 3.43-3.49 (m, 1H), 3.71-3.77 (m, 1H), 3.94-4.08 (m, 4H), 4.24 (d, 1H), 5.04 (m, 1H), 7.13 (t, 1H), 7.38 (m, 2H), 7.62-7.68 (m, 2H), 7.94 (d, 1H), 8.35 (s, 1H). MS (+ESI) m/z 451 (MH+).

Workup

  1. extractionextracted with EtOAc
  2. extractionThe EtOAc extract
  3. washwas washed with water
  4. additiondiluted twice with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-419b767916114e2c92ac8fb7120baa56
Source dataset
uspto-grants-2010_09
Patent number
US07799787B2

Reaction notes

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