Potassium Carbonate → 2-Hydroxy-N-methyl-N-{2-[(4-{3-methyl-4-(pyridin-2-ylmethoxy)anilino}quinazolin-5-yl)oxy]ethyl}acetamide

HRID 1864190Notes

Reaction equation

HRID 1864190 reaction equation
[OH:1][CH2:2][C:3]([N:5]([CH2:7][CH2:8][O:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[C:12]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[C:23]([CH3:28])[CH:22]=1)=[N:13][CH:14]=[N:15]2)[CH3:6])=[O:4].Cl.[N:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH2:36]Cl.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C=O)C>[OH:1][CH2:2][C:3]([N:5]([CH3:6])[CH2:7][CH2:8][O:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[C:12]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH2:36][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][N:30]=3)=[C:23]([CH3:28])[CH:22]=1)=[N:13][CH:14]=[N:15]2)=[O:4]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 23392Picolyl chloride hydrochlorideHCID 2855718-Crown-6HCID 690579972-Hydroxy-N-[2-({4-[4-hydroxy-3-methylanilino]quinazolin-5-yl}oxy)ethyl]-N-methylacetamide

Product 1

HCID 113973342-Hydroxy-N-methyl-N-{2-[(4-{3-methyl-4-(pyridin-2-ylmethoxy)anilino}quinazolin-5-yl)oxy]ethyl}acetamideYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Hydroxy-N-[2-({4-[4-hydroxy-3-methylanilino]quinazolin-5-yl}oxy)ethyl]-N-methylacetamide (100 mg), picolyl chloride hydrochloride (60 mg) and potassium carbonate (120 mg) were stirred in DMF (5 ml) to which was added 18-crown-6 (10 mg). The reaction was stirred at room temperature for 2 days. The DMF was removed in vacuo, water (5 ml) was added and then the suspension was extracted with DCM (2×5 ml). The DCM fraction was purified by chromatography using 2.5-5% of 10:1 DCM/methanol containing 0.5% ammonia (0.880) as eluent. The appropriate fractions were evaporated, and the residue was precipitated from DCM/diethyl ether to give the title product as a light yellow solid (28 mg, 23%); NMR spectrum (DMSO-d6, 100° C.) 2.29 (s, 3H), 3.00 (s, 3H), 3.90 (t, 2H), 4.16 (s, 2H), 4.50 (t, 2H), 5.20 (s, 2H), 7.01 (d, 1H), 7.16 (d, 1H), 7.34 (d, 2H), 7.51 (m, 2H), 7.55 (d, 1H), 7.79 (t, 1H), 7.83 (td, 1H), 8.41 (s, 1H), 8.57 (d, 1H), 9.62 (s, 1H); Mass spectrum MH+ 474.

Workup

  1. customThe DMF was removed in vacuo, water (5 ml)
  2. additionwas added
  3. extractionthe suspension was extracted with DCM (2×5 ml)
  4. customThe DCM fraction was purified by chromatography
  5. customThe appropriate fractions were evaporated
  6. customthe residue was precipitated from DCM/diethyl ether

Sources & evidence

ORD record
ord-c8bae81f5b754747bdbb3b9d881e34d7
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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