4-Methylmorpholine → But-2-ynoic acid [5-(3-bromo-phenylamino)-6-cyano-[1,8]naphthyridin-3-yl]-amide

HRID 1266260Notes

Reaction equation

HRID 1266260 reaction equation
[C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[N:31][CH:32]=1)[N:29]=[CH:28][C:27]([C:33]#[N:34])=[C:26]2[NH:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Br:42])[CH:37]=1>O1CCCC1.N1C=CC=CC=1>[Br:42][C:38]1[CH:37]=[C:36]([NH:35][C:26]2[C:27]([C:33]#[N:34])=[CH:28][N:29]=[C:30]3[C:25]=2[CH:24]=[C:23]([NH:22][C:1](=[O:6])[C:2]#[C:3][CH3:4])[CH:32]=[N:31]3)[CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 685352-Butynoic acidHCID 99498136-Amino-4-(3-bromo-phenylamino)-[1,8]naphthyridine-3-carbonitrile

Product 1

HCID 15550658But-2-ynoic acid [5-(3-bromo-phenylamino)-6-cyano-[1,8]naphthyridin-3-yl]-amideYield 29.8%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.85 g (10.1 mmol) of tetrolic acid and 1.8 g (17.96 mmol) of N-methyl morpholine in 18 ml of tetrahydrofuran was stirred at 0° C. as 1.35 g (9.9 mmol) of isobutyl chloroformate was slowly added. After 15 min, this mixture was added to a solution of 1.3 g (3.8 mmol) of 6-amino-4-(3-bromo-phenylamino)-[1.8]naphthyridine-3-carbonitrile and 5 mg of 4-N,N-dimethylamino-pyridine in 10 ml pyridine. The mixture was stirred a room temperature for 2.25 hr. The tetrahydrofuran was removed, diluted sodium bicarbonate was added, and the solid was collected via filtration. The solid was air dried and chromatographed on silica gel eluting with ethyl acetate-methanol mixtures giving 0.46 g of the title compound as a tan powder: mass spectrum (electrospray, m/e): M+H 408.1, 406.0.

Workup

  1. additionwas slowly added
  2. customThe tetrahydrofuran was removed
  3. additiondiluted sodium bicarbonate was added
  4. filtrationthe solid was collected via filtration
  5. customdried
  6. customchromatographed on silica gel eluting with ethyl acetate-methanol

Sources & evidence

ORD record
ord-3b8139a5154946b2ab5a77ae6d0ae92a
Source dataset
uspto-grants-2003_04
Patent number
US06548496B2

Reaction notes

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