Methylamine → 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-N,4-dimethylbenzamide

HRID 1867117Notes

Reaction equation

HRID 1867117 reaction equation
[Cl:1][C:2]1[C:3](=[O:29])[N:4]([C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=2[CH3:28])[C:22](O)=[O:23])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].CN.C1COCC1.C[CH2:38][N:39]=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:3](=[O:29])[N:4]([C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=2[CH3:28])[C:22]([NH:39][CH3:38])=[O:23])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

8

Reactant 6

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 220510673-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic acid

Product 1

HCID 220506953-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-N,4-dimethylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared from 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic acid (from step 1 above) (1.5 g, 3.57 mmol) in dichloromethane (35 ml). To this mixture, 2.0 M methyl amine in THF (3.6 ml, 7.14 mmol) was added, followed, in order, by EDCI (0.67 g, 4.28 mmol), 1-hydroxybenzotriazole (0.58 g, 4.28 mmol) and triethylamine (0.99 ml, 7.14 mmol). The reaction was stirred at room temperature overnight. The reaction was quenched with NH4Cl and extracted 3 times with ethyl acetate. The combined organic layer was then washed with saturated NaHCO3 (aq.) and extracted 3 times with ethyl acetate. The organic layers were combined and washed with H2O and extracted 3 times with ethyl acetate. The organic layers were combined and dried over Na2SO4 and evaporated. The resulting residue was triturated with diethyl ether/hexane to obtain a solid, which was dried in vacuo to give a white solid (1.5 g, 72%). 1H NMR (300 MHz, CD3OD) δ 7.90 (dd, J=8.06, 1.81 Hz, 1H), 7.67 (app q, J=6.44 Hz, 1H), 7.55 (d, J=8.06 Hz, 1H), 7.13-7.06 (m, 2H), 6.74 (s, 1H), 5.40 (s, 2H), 2.93 (s, 3H), 2.13 (s, 3H), 2.04 (s, 3H); ES-MS m/z 433 (M+H). ES-HRMS m/z 433.1153 (M+H calcd for C22H20ClF2N2O3 requires 433.1125).

Workup

  1. customThe reaction was quenched with NH4Cl
  2. extractionextracted 3 times with ethyl acetate
  3. washThe combined organic layer was then washed with saturated NaHCO3 (aq.)
  4. extractionextracted 3 times with ethyl acetate
  5. washwashed with H2O
  6. extractionextracted 3 times with ethyl acetate
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customThe resulting residue was triturated with diethyl ether/hexane
  10. customto obtain a solid, which
  11. customwas dried in vacuo

Sources & evidence

ORD record
ord-baeb2fbabb3543fb94b4c3cd4cb0fdcd
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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