Glycolic Acid → 2-Hydroxy-N-[2-({4-[4-hydroxy-3-methylanilino]quinazolin-5-yl}oxy)ethyl]-N-methylacetamide

HRID 1864192Notes

Reaction equation

HRID 1864192 reaction equation
[C:1]([OH:5])(=O)[CH2:2][OH:3].[CH3:6][C:7]1[CH:12]=[C:11]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][C:22]=3[O:24][CH2:25][CH2:26][NH:27][CH3:28])[N:17]=[CH:16][N:15]=2)[CH:10]=[CH:9][C:8]=1[OH:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:3][CH2:2][C:1]([N:27]([CH2:26][CH2:25][O:24][C:22]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:23]=1[C:14]([NH:13][C:11]1[CH:10]=[CH:9][C:8]([OH:29])=[C:7]([CH3:6])[CH:12]=1)=[N:15][CH:16]=[N:17]2)[CH3:28])=[O:5]

Participants

5

Reactant 3

HCID 757Glycolic AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 690540072-Methyl-4-({5-[2-(methylamino)ethoxy]quinazolin-4-yl}amino)phenol

Product 1

HCID 690579972-Hydroxy-N-[2-({4-[4-hydroxy-3-methylanilino]quinazolin-5-yl}oxy)ethyl]-N-methylacetamideYield 86.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of glycolic acid (100 mg) in DMF (2 ml) was added dropwise to a solution of 2-methyl-4-({5-[2-(methylamino)ethoxy]quinazolin-4-yl}amino)phenol (400 mg) in DMF (4 ml) and the mixture held under sonication for 5 minutes. A solution of HATU (519 mg) in DMF (2 ml) was then added and the solution was stirred at ambient temperature for 16 hours, and then concentrated in vacuo. The residue was treated with water to precipitate a brown solid that was collected by filtration, and washed with water to give 2-hydroxy-N-[2-({4-[4-hydroxy-3-methylanilino]quinazolin-5-yl}oxy)ethyl]-N-methylacetamide as a brown solid (406 mg, 86%); NMR spectrum (DMSO-d6) 2.15 (s, 3H), 2.94 (s, 3H), 3.87 (m, 2H), 4.04 (s, 2H), 4.48 (m, 2H), 6.81 (d, 1H), 7.20 (dd, 1H), 7.25 (d, 1H), 7.35 (m, 2H), 7.92 (t, 1H), 8.64 (s, 1H), 9.46 (s, 1H), 10.49 (s, 1H); Mass spectrum M+ 383.

Workup

  1. customthe mixture held under sonication for 5 minutes
  2. concentrationconcentrated in vacuo
  3. additionThe residue was treated with water
  4. customto precipitate a brown solid
  5. filtrationthat was collected by filtration
  6. washwashed with water

Sources & evidence

ORD record
ord-a3c792961d67464e84e2030467c14ad2
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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