4-Methylmorpholine → Isopropyl-methyl-amino-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide

HRID 1068992Notes

Reaction equation

HRID 1068992 reaction equation
ClC(OCC(C)C)=O.CN1CCOCC1.[CH:16]([C:19]([CH3:26])([NH2:25])[C:20]#[C:21][C:22]([OH:24])=O)([CH3:18])[CH3:17].[Br:27][C:28]1[CH:29]=[C:30]([NH:34][C:35]2[C:44]3[C:39](=[CH:40][CH:41]=[C:42]([NH2:45])[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1>O1CCCC1.N1C=CC=CC=1>[Br:27][C:28]1[CH:29]=[C:30]([NH:34][C:35]2[C:44]3[C:39](=[CH:40][CH:41]=[C:42]([NH:45][C:22](=[O:24])[C:21]#[C:20][C:19]([CH:16]([CH3:17])[CH3:18])([CH3:26])[NH2:25])[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamineHCID 21190750Isopropyl-methyl-amino-but-2-ynoic acid

Product 1

HCID 86757052Isopropyl-methyl-amino-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amideYield 40.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

Isobutyl chloroformate (0.845 g, 6.2mmol) and N-methylmorpholine (1.0 g, 9.9 mmol) were added to an ice cold solution of 1.5 g (9.67 mmol) of isopropyl-methyl-amino-but-2-ynoic acid in 70 mL of tetrahydrofuran under nitrogen. After stirring for 30 min, a solution of 1.500 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 15 mL of pyridine was added and the mixture was stirred for 2 hr at 0° C. The reaction was then quenched with ice water, poured into saturated sodium bicarbonate, and the product was extracted with ethyl acetate. Chromatography of the extract on silica gel, eluting with methanol/ethyl acetate (15:85), gave 0.870 g of isopropyl-methyl-amino-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide: mass spectrum (m/e): M+H 452.

Workup

  1. stirringthe mixture was stirred for 2 hr at 0° C
  2. customThe reaction was then quenched with ice water
  3. additionpoured into saturated sodium bicarbonate
  4. extractionthe product was extracted with ethyl acetate
  5. extractionChromatography of the extract on silica gel
  6. washeluting with methanol/ethyl acetate (15:85)

Sources & evidence

ORD record
ord-482ef4ddf1a34241a03f9f9a65d96501
Source dataset
uspto-grants-2001_06
Patent number
US06251912B1

Reaction notes

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