4-Methylmorpholine → 4-(4-Methyl-piperazin-1-yl)-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide

HRID 1068987Notes

Reaction equation

HRID 1068987 reaction equation
ClC(OCC(C)C)=O.CN1CCOCC1.[CH3:16][N:17]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]#[C:25][C:26]([OH:28])=O)[CH2:19][CH2:18]1.[Br:29][C:30]1[CH:31]=[C:32]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([NH2:47])[CH:45]=3)[N:40]=[CH:39][N:38]=2)[CH:33]=[CH:34][CH:35]=1>N1C=CC=CC=1.O1CCCC1>[Br:29][C:30]1[CH:31]=[C:32]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([NH:47][C:26](=[O:28])[C:25]#[C:24][CH2:23][N:20]4[CH2:19][CH2:18][N:17]([CH3:16])[CH2:22][CH2:21]4)[CH:45]=3)[N:40]=[CH:39][N:38]=2)[CH:33]=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamineHCID 185489814-(4-Methylpiperazin-1-yl)but-2-ynoic acid

Product 1

HCID 102774084-(4-Methyl-piperazin-1-yl)-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amideYield 25.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

Isobutyl chloroformate (0.905 g, 6.6 mmol) and N-methylmorpholine (1.550 g, 15.3 mmol) were added to an ice cold solution of 1.900 g (10.71 mmol) of 4-(4-methyl-piperazin-1-yl)-but-2-ynoic acid in l50 mL of tetrahydrofuran under nitrogen. After stirring for 30 min, a solution of 1.500 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 12 mL of pyridine was added and the mixture was stirred for 2 hr at 0° C. The reaction was then quenched with ice water, then it was 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 0.590 g of 4-(4-methyl-piperazin-1-yl) -but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide: mass spectrum (m/e): M+H 479.

Workup

  1. stirringthe mixture was stirred for 2 hr at 0° C
  2. customThe reaction was then quenched with ice water
  3. additionit was poured 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-3c0727e8d3d64f29a7ecbf40bedb6d78
Source dataset
uspto-grants-2001_06
Patent number
US06251912B1

Reaction notes

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