Triethylamine → 2-(4-(4-Methoxybenzoyl)piperidinylcarbonyl)-4-methyl-5-bromopyridine

HRID 1480536Notes

Reaction equation

HRID 1480536 reaction equation
[Br:1][C:2]1[C:3]([CH3:11])=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.Cl.[CH3:13][O:14][C:15]1[CH:28]=[CH:27][C:18]([C:19]([CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[O:20])=[CH:17][CH:16]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH3:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([C:19]([CH:21]2[CH2:26][CH2:25][N:24]([C:8]([C:5]3[CH:4]=[C:3]([CH3:11])[C:2]([Br:1])=[CH:7][N:6]=3)=[O:10])[CH2:23][CH2:22]2)=[O:20])=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27405874-(4-Methoxybenzoyl)piperidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 457900315-Bromo-4-methylpyridine-2-carboxylic acid

Product 1

HCID 897252122-(4-(4-Methoxybenzoyl)piperidinylcarbonyl)-4-methyl-5-bromopyridineYield 89.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-bromo-4-methylpyridine-2-carboxylic acid (0.400 g, 1.85 mmol, 1.0 eq) and 4-(4-methoxybenzoyl)piperidine hydrochloride (0.474 g, 1.85 mmol, 1.0 eq) was added dimethylformamide (10 mL) followed by triethylamine (0.64 mL, 4.36 mmol, 2.5 eq). HATU (0.774 g, 2.04 mmol, 1.1 eq) was added forming a yellow solution, which was stirred at room temperature for 1 day. The reaction was partitioned between EtOAc (120 mL) and water-NaHCO3 (1:1, 120 mL). The organics were further washed with brine (120 mL), water (120 mL) and brine (100 mL), dried (Na2SO4) and concentrated under reduced pressure. MPLC (0→10% MeOH—CH2Cl2) yielded the title compound (0.693 g, 89%) as a yellow oil; 1H nmr (CDCl3) δ 8.55 (1H, s, pyH-3 or H-6), 7.90 (2H, d, J 9.0 Hz, 2H of C6H4OMe), 7.48 (1H, s, pyH-3 or H-6), 6.91 (2H, d, J 9.0 Hz, 2H of C6H4OMe), 4.64 (1H, m, 1H of BzpipH-2, H-6), 4.01 (1H, m, 1H of BzpipH-2, H-6), 3.83 (3H, s, OCH3), 3.49 (1H, m, BzpipH-4), 3.23 (1H, m, 1H of BzpipH-2, H-6), 3.03 (1H, m, 1H of BzpipH-2, H-6), 2.39 (3H, s, pyCH3), 1.95 (1H, m, 1H of BzpipH-3, H-5), 1.86-1.75 (3H, s, 3H of BzpipH-3, H-5); m/z 417, 419 [M+H]+.

Workup

  1. customforming a yellow solution, which
  2. customThe reaction was partitioned between EtOAc (120 mL) and water-NaHCO3 (1:1, 120 mL)
  3. washThe organics were further washed with brine (120 mL), water (120 mL) and brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ee93ab24cbd74e06a29cdd4252256880
Source dataset
uspto-grants-2016_08
Patent number
US09409884B2

Reaction notes

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