Methylamine → N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-6-((methylamino)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777917Notes

Reaction equation

HRID 1777917 reaction equation
Cl.CN.CN.[BH3-][C:7]#[N:8].[Na+].[C:10]([C:12]1[CH:13]=[CH:14][C:15]([NH:18][C:19]([N:21]2[C:30]3[C:25](=[CH:26][C:27]([CH:36]=O)=[C:28]([CH:31]([O:34][CH3:35])[O:32][CH3:33])[N:29]=3)[CH2:24][CH2:23][CH2:22]2)=[O:20])=[N:16][CH:17]=1)#[N:11]>CO>[C:10]([C:12]1[CH:13]=[CH:14][C:15]([NH:18][C:19]([N:21]2[C:30]3[C:25](=[CH:26][C:27]([CH2:36][NH:8][CH3:7])=[C:28]([CH:31]([O:34][CH3:35])[O:32][CH3:33])[N:29]=3)[CH2:24][CH2:23][CH2:22]2)=[O:20])=[N:16][CH:17]=1)#[N:11]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 5003444Sodium cyanoborohydrideHCID 6364545Methylamine hydrochlorideHCID 118037054N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-6-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×

Product 1

HCID 118036882N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-6-((methylamino)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A tube was charged with methylamine hydrochloride (7.79 mg, 0.115 mmol) followed by methylamine (2 M in MeOH, 0.058 ml, 0.115 mmol) and NaCNBH3 (14.5 mg, 0.231 mmol). Then, a suspension of N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-6-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 36, 22 mg, 0.058 mmol) in MeOH (1 ml) was added, the tube was sealed and the reaction mixture was stirred at 70° C. for 1 h. The reaction mixture was quenched with water and concentrated until the organic solvents had mostly been removed. Water was added and the mixture was extracted with DCM (3×). The organic phase was then dried over Na2SO4, filtered and evaporated. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, DCM/(DCM/(7 M NH3 in MeOH) 9/1) 100:0 to 50:50) to give the title compound as a yellow resin. (UPLC-MS 3) tR 0.72 min; ESI-MS 397.3 [M+H]+.

Workup

  1. additionwas added
  2. customthe tube was sealed
  3. customThe reaction mixture was quenched with water
  4. concentrationconcentrated until the organic solvents
  5. customhad mostly been removed
  6. additionWater was added
  7. extractionthe mixture was extracted with DCM (3×)
  8. dry with materialThe organic phase was then dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, DCM/(DCM/(7 M NH3 in MeOH) 9/1) 100:0 to 50:50)

Sources & evidence

ORD record
ord-f1f56d2290a841d0839587f5b717d0b2
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

Loading…