Morpholine → HCID 69194223, compound

HRID 2180980Notes

Reaction equation

HRID 2180980 reaction equation
Cl[CH2:2][CH:3]=[CH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][N:9]=[C:8]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=2)=[C:18]([CH3:29])[CH:17]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.C(N(CC)CC)C>C1COCC1>[CH3:29][C:18]1[CH:17]=[C:16]([NH:15][C:8]2[C:7]3[C:12](=[CH:13][CH:14]=[C:5]([CH:4]=[CH:3][CH2:2][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[CH:6]=3)[N:11]=[CH:10][N:9]=2)[CH:21]=[CH:20][C:19]=1[O:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 69116176HCID 69116176, compound

Product 1

HCID 69194223HCID 69194223, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a suspension of 0.035 g (0.091 mmol) of 3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-en-1-ol in 0.5 mL of methylene chloride and 1 mL of ethylene dichloride was added 1 mL of thionyl chloride. The reaction was heated at 100° C. for 1 hour and the solvents were evaporated to provide [6-(3-chloro-propenyl)-quinazolin-4-yl]-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amine [MS: M+ 403.1] which was dissolved in THF and used directly in the next reaction. To the solution of [6-(3-chloro-propenyl)-quinazolin-4-yl]-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amine was added 0.10 mL of morpholine and 0.044 mL of triethylamine. The mixture was heated at 85° C. for 16 hours, cooled to room temperature, and partitioned between 10% aqueous potassium carbonate and ethyl acetate. The aqueous layer was further extracted with ethyl acetate and the combined organics were dried and evaporated to yield 57 mg of material. The product was purified on a silica gel prep plate, eluting with 96:4:0.1 chloroform/methanol/concentrated ammonium hydroxide to afford 26 mg of the title compound; 1H NMR (CDCl3): δ 8.71 (s, 1), 8.33 (m, 2), 7.94 (s, 1), 7.80 (m, 2), 7.69 (s, 1), 7.58 (m, 1), 7.20 (m, 1), 6.94 (d, J8.7 Hz, 1), 6.68 (d, J=15.8 Hz, 1), 6.46 (m, 1), 3.79 (m, 4), 3.26(m, 2), 2.63 (m, 4), 2.25 (s, 3).

Workup

  1. customused directly in the next reaction
  2. temperaturecooled to room temperature
  3. custompartitioned between 10% aqueous potassium carbonate and ethyl acetate
  4. extractionThe aqueous layer was further extracted with ethyl acetate
  5. customthe combined organics were dried
  6. customevaporated

Sources & evidence

ORD record
ord-58836a03ce264d91a304ad8826b299fd
Source dataset
uspto-grants-2005_05
Patent number
US06890924B2

Reaction notes

Loading…