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

HRID 1777882Notes

Reaction equation

HRID 1777882 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:8]([C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][N:21]=1)=[O:18])[CH2:7][CH2:6][CH2:5]2.[Li]C.[Li]CCCC.CN([CH:38]=[O:39])C.[NH4+].[Cl-]>C1COCC1.CCCCCC>[C:26]([C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:17]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([CH:38]=[O:39])=[C:11]([CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:10]=3)[CH2:5][CH2:6][CH2:7]2)=[O:18])=[N:21][CH:22]=1)#[N:27]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 1180363436-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×HCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 118037054N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-6-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 6-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 2H, 300 mg, 0.694 mmol) in THF (10 ml) at −78° C., was added MeLi (1.6 M in Et2O, 0.434 ml, 0.694 mmol), the solution was stirred for 5 min, then n-BuLi in (1.6 M in hexane, 0.477 ml, 0.763 mmol) was added and the solution was stirred for 20 min. Then, DMF (0.322 ml, 4.16 mmol) was added, the reaction mixture was stirred at −78° C. for 1 h and then allowed to warm to room temperature. The reaction mixture was poured into sat. aq. NH4Cl and extracted twice with DCM. The combined organic phase was then dried over Na2SO4, filtered and evaporated. The crude material was purified by normal phase chromatography (40 g gold silica gel cartridge, heptanes/EtOAc 95:5 to 0:100) to give the title compound as a colorless powder. (UPLC-MS 3) tR 1.10 min; ESI-MS 382.2 [M+H]+.

Workup

  1. stirringthe solution was stirred for 20 min
  2. stirringthe reaction mixture was stirred at −78° C. for 1 h
  3. extractionextracted twice with DCM
  4. dry with materialThe combined organic phase was then dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude material was purified by normal phase chromatography (40 g gold silica gel cartridge, heptanes/EtOAc 95:5 to 0:100)

Sources & evidence

ORD record
ord-31eca67211594651b9fdbfbd4a084a88
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

Loading…