4-Methylmorpholine → N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}-4-(4-ethylpiperazin-1-yl)but-2-ynamide

HRID 1068981Notes

Reaction equation

HRID 1068981 reaction equation
ClC(OCC(C)C)=O.CN1CCOCC1.[CH2:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[C:26][C:27]([OH:29])=O)[CH2:20][CH2:19]1)[CH3:17].[Br:30][C:31]1[CH:32]=[C:33]([NH:37][C:38]2[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([NH2:48])[CH:46]=3)[N:41]=[CH:40][N:39]=2)[CH:34]=[CH:35][CH:36]=1>O1CCCC1.N1C=CC=CC=1>[Br:30][C:31]1[CH:32]=[C:33]([NH:37][C:38]2[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([NH:48][C:27](=[O:29])[C:26]#[C:25][CH2:24][N:21]4[CH2:20][CH2:19][N:18]([CH2:16][CH3:17])[CH2:23][CH2:22]4)[CH:46]=3)[N:41]=[CH:40][N:39]=2)[CH:34]=[CH:35][CH:36]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamineHCID 118056494-(N-ethylpiperazino)-2-butynoic acid

Product 1

HCID 5328964N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}-4-(4-ethylpiperazin-1-yl)but-2-ynamideYield 61.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

Isobutyl chloroformate (0.847 g, 6.2 mmol) and N-methylmorpholine (1.460 g, 14.4 mmol) were added to an ice cold solution of 1.900 g (9.52 mmol) of 4-(4-ethyl-piperazin-1-yl)-but-2-ynoic acid in 50 mL of tetrahydrofuran under nitrogen. After stirring for 30 min, a solution of 1.500 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 10 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 (30:70), gave 1.450 g of 4-(4-Ethyl-piperazin-1-yl)-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide: mass spectrum (m/e): M+H 493.

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 (30:70)

Sources & evidence

ORD record
ord-7fcb91f9ae9f4e7aa631184e0fe3a822
Source dataset
uspto-grants-2001_06
Patent number
US06251912B1

Reaction notes

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