1,2-Dichloroethane → 5-chloro-N-((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)-2-methyl-3-((1-methylpiperidin-4-yl)oxy)benzamide

HRID 1050469Notes

Reaction equation

HRID 1050469 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:13][CH:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9]C)=O.[OH-].[Na+].Cl.[NH2:24][CH2:25][C:26]1[C:31](=[O:32])[CH:30]=[C:29]([CH3:33])[NH:28][C:27]=1[CH3:34].ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1.C(=O)(O)[O-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([O:13][CH:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([NH:24][CH2:25][C:26]1[C:31](=[O:32])[CH:30]=[C:29]([CH3:33])[NH:28][C:27]=1[CH3:34])=[O:9]

Participants

9

Reactant 7

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 90273068Methyl 5-chloro-2-methyl-3-((1-methylpiperidin-4-yl)oxy)benzoateHCID 902732273-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one hydrochloride

Product 1

HCID 769023365-chloro-N-((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)-2-methyl-3-((1-methylpiperidin-4-yl)oxy)benzamideYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 5-chloro-2-methyl-3-((1-methylpiperidin-4-yl)oxy)benzoate (120 mg, 0.403 mmol) in MeOH (2 mL) was treated with 6 N NaOH (2 mL). The reaction was stirred for 2 h at RT, at which time it was concentrated in vacuo. The residue was suspended in water, acidified with 6 N HCl, filtered and dried. The resultant product was dissolved in DMF (4.0 mL) and treated with 3-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one, hydrochloride (76 mg, 0.403 mmol), 1-hydroxy-7-azabenzotriazole (HOAT) (82 mg, 0.604 mmol), EDC (116 mg, 0.604 mmol) and N-methylmorpholine (177 μl, 1.612 mmol). The reaction was stirred for 3 h at RT, at which time it was poured into saturated sodium bicarbonate solution and extracted with DCM (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to give 5-chloro -N-((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)-2-methyl-3-((1-methylpiperidin -4-yl)oxy)benzamide (0.050 g, 0.120 mmol, 30% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.54-1.74 (m, 2 H) 1.80-1.94 (m, 2 H) 2.06 (s, 3 H) 2.12-2.22 (m, 6 H) 2.25 (d, J=9.60 Hz, 2 H) 2.31 (s, 3 H) 4.19 (d, J=5.05 Hz, 2 H) 4.48 (br. s., 1 H) 5.87 (s, 1 H) 6.79 (d, J=2.02 Hz, 1 H) 7.10 (d, J=2.02 Hz, 1 H) 8.21 (t, J=4.93 Hz, 1 H) 11.00 (s, 1 H). MS(ES) [M+H]+ 418.3.

Workup

  1. concentrationwas concentrated in vacuo
  2. filtrationfiltered
  3. customdried
  4. dissolutionThe resultant product was dissolved in DMF (4.0 mL)
  5. stirringThe reaction was stirred for 3 h at RT, at which time it
  6. extractionextracted with DCM (3×25 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-54a8f13ef3d24704983251b2d24cdc03
Source dataset
uspto-grants-2016_07
Patent number
US09382234B2

Reaction notes

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