Dimethylamine → 4-Dimethylamino-but-2-enoic acid [5-(3-bromo-phenylamino)-6-cyano-[1,8]naphthyridin-3-yl]-amide

HRID 1266262Notes

Reaction equation

HRID 1266262 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Br:21])[CH:16]=1.Br[CH2:23][CH:24]=[CH:25][C:26](Cl)=[O:27].[CH3:29][N:30]1CCC[C:31]1=O.CNC>O1CCCC1>[Br:21][C:17]1[CH:16]=[C:15]([NH:14][C:5]2[C:6]([C:12]#[N:13])=[CH:7][N:8]=[C:9]3[C:4]=2[CH:3]=[C:2]([NH:1][C:26](=[O:27])[CH:25]=[CH:24][CH2:23][N:30]([CH3:31])[CH3:29])[CH:11]=[N:10]3)[CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 13387N-methyl-2-pyrrolidoneHCID 99498136-Amino-4-(3-bromo-phenylamino)-[1,8]naphthyridine-3-carbonitrileHCID 536352004-Bromo-but-2-enoyl chloride

Product 1

HCID 698496924-Dimethylamino-but-2-enoic acid [5-(3-bromo-phenylamino)-6-cyano-[1,8]naphthyridin-3-yl]-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 2.5 g (7.35 mmol) of 6-amino-4-(3-bromo-phenylamino)-[1.8]naphthyridine-3-carbonitrile and 0.95 g (7.35 mmol) of disopropylethyl amine in 40 ml tetrahydrofuran at 0° C. , with stirring, was added 1.42 g (7.72 mmol) of 4-bromo-2-butenoyl chloride followed by 5 ml of N-methyl pyrrolidone. After 1 hr, 55 ml of 2M dimethylamine in tetrahydrofuran was added. After 30 min, the solvents were removed. The mixture was mixed with ethyl acetate and saturated sodium bicarbonate. The organic layer was dried over magnesium sulfate and the solvent was removed. The product was purified by chromatography on silica gel eluting first with ethyl acetate-methanol 9:1 to remove less polar impurities and then with acetate-methanol-triethyl amine 40:10:1 to elute 0.49 g of the product which was obtained as and orange powder: mass spectrum (electrospray, m/e): M+H 450.9,453.0; (M+2H)+2 226.7, 225.8.

Workup

  1. waitAfter 30 min
  2. customthe solvents were removed
  3. additionThe mixture was mixed with ethyl acetate and saturated sodium bicarbonate
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. customthe solvent was removed
  6. customThe product was purified by chromatography on silica gel eluting first with ethyl acetate-methanol 9:1
  7. customto remove less polar impurities
  8. washwith acetate-methanol-triethyl amine 40:10:1 to elute 0.49 g of the product which
  9. customwas obtained as and orange powder

Sources & evidence

ORD record
ord-0ea32607a57a4e24b8808658e973a485
Source dataset
uspto-grants-2003_04
Patent number
US06548496B2

Reaction notes

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