Isobutyl chloroformate → But-2-ynoic acid, [4-(3-bromo-phenylamino)-3-cyano-[1,7]naphthyridin-6-yl]-amide

HRID 276859Notes

Reaction equation

HRID 276859 reaction equation
[C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].ClC(OCC(C)C)=O.[NH2:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][N:25]=1)[N:22]=[CH:21][C:20]([C:26]#[N:27])=[C:19]2[NH:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Br:35])[CH:30]=1.C(Cl)(=O)C#CC>O1CCCC1.N1C=CC=CC=1>[Br:35][C:31]1[CH:30]=[C:29]([NH:28][C:19]2[C:18]3[C:23](=[CH:24][N:25]=[C:16]([NH:15][C:1](=[O:6])[C:2]#[C:3][CH3:4])[CH:17]=3)[N:22]=[CH:21][C:20]=2[C:26]#[N:27])[CH:34]=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 62365Isobutyl chloroformateHCID 685352-Butynoic acidHCID 97980066-Amino-4-(3-bromo-phenylamino)-[1,7]naphthyridine-3-carbonitrileHCID 12714994But-2-ynoyl chloride

Product 1

HCID 57267484But-2-ynoic acid, [4-(3-bromo-phenylamino)-3-cyano-[1,7]naphthyridin-6-yl]-amideYield 8.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 100 mg of butynoic acid in 5 mL of anhydrous tetrahydrofuran under an inert atmosphere at 0° C. was added 0.23 mL on N-methyl morpholine and 0.15 mL of isobutyl chloroformate. This solution was then added to 150 mg of 6-amino-4-(3-bromo-phenylamino)-[1.7]naphthyridine-3-carbonitrile in 3 mL of pyridine at 0° C. After standing at 0° C. for three days, a second portion of butynoyl chloride was added. After an additional 8 hours the reaction was stripped of solvents on a rotary evaporator and the crude product was purified by flash chromatograph using a gradient of 0-20% methanol/chloroform to give 15 mg of but-2-ynoic acid, [4-(3-bromo-phenylamino)-3-cyano-[1.7]naphthyridin-6-yl]-amide: melting point 255° C. (decomposed); mass spectrum (m/e): M+H 406.1, 408.2.

Workup

  1. customAfter an additional 8 hours the reaction was stripped of solvents on a rotary evaporator
  2. customthe crude product was purified by flash chromatograph

Sources & evidence

ORD record
ord-c42d2ee735ca4af78f7be2183409aa3c
Source dataset
uspto-grants-2002_03
Patent number
US06355636B1

Reaction notes

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