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

HRID 1069004Notes

Reaction equation

HRID 1069004 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]#[C:8][C:9]([OH:11])=O.ClC(OCC(C)C)=O.CN1CCOCC1.[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.C(=O)(O)[O-].[Na+]>O1CCCC1>[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:9](=[O:11])[C:8]#[C:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamineHCID 110948894-(2-Methoxy-ethoxy)-but-2-ynoic acid

Product 1

HCID 5328966N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}-4-(2-methoxyethoxy)but-2-ynamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 0.72 g of 4-(2-Methoxy-ethoxy)-but-2-ynoic acid and 0.57 mL of isobutyl chloroformate in 15 mL of tetrahydrofuran at 0° C. was added 0.5 mL of N-methylmorpholine followed by 1.2 g of solid N-(3-bromophenyl)-4,6-quinazolindiamine. Stirring was continued for 1 hr at 0° C. and 30 min at room temperature. The mixture was stored over night at −10° C. The mixture was poured into saturated sodium bicarbonate and extracted with ethyl acetate. The organic solution was dried over magnesium sulfate. The solvent was removed and the residue was chromatographed on silica gel eluting with ethyl acetate, choroform, and methanol solvent mixtures to give 0.55 g of 4-(2-Methoxy-ethoxy)-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide as a yellow solid: mass spectrum (m/e): M+H 454.9, 456.9.

Workup

  1. waitThe mixture was stored over night at −10° C
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic solution was dried over magnesium sulfate
  4. customThe solvent was removed
  5. customthe residue was chromatographed on silica gel eluting with ethyl acetate, choroform, and methanol solvent mixtures

Sources & evidence

ORD record
ord-a09212a4d49645f18b36547dbdc4f442
Source dataset
uspto-grants-2001_06
Patent number
US06251912B1

Reaction notes

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