Diisopropylethylamine → 4-chloro-N-(1-methylpiperidin-4-yl)picolinamide

HRID 626589Notes

Reaction equation

HRID 626589 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH2:8])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Cl.[Cl:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26](Cl)=[O:27])[CH:21]=1>C1COCC1.CCOC(C)=O>[Cl:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]([NH:8][CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[O:27])[CH:21]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 223972704-Chloropyridine-2-carbonyl chloride--hydrogen chloride (1/1)

Product 1

HCID 432166324-chloro-N-(1-methylpiperidin-4-yl)picolinamideYield 112%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 0° C. solution of 1-methyl-4-amino-piperidine (0.860 g, 7.53 mmol) and DIEA (2.63 mL, 15.06 mmol) in THF (15 mL) was treated with 4-chloropicolinoyl chloride hydrochloride (0.8 g, 3.77 mmol) in one portion, stirred at RT for 2 h, diluted with EtOAc and washed with satd. NaHCO3, then brine. The organic layer was dried over Na2SO4 and concentrated to dryness to afford 4-chloro-N-(1-methylpiperidin-4-yl)picolinamide (1.07 g, 112%). 1H NMR (400 MHz, DMSO-d6): δ 8.61-8.60 (m, 2H), 8.00 (d, J=2.1 Hz, 1H), 7.75 (dd, J=5.3, 2.2 Hz, 1H), 3.74-3.72 (m, 1H), 2.71 (d, J=11.3 Hz, 2H), 2.13 (s, 3H), 1.93 (m, 2H), 1.69-1.67 (m, 4H); MS (ESI) m/z: 254.1 (M+H+).

Workup

  1. washwashed with satd
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-94e02388105c4217a5de7a24be93abf1
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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