Toluene → HCID 69116274, compound

HRID 2055156Notes

Reaction equation

HRID 2055156 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[C:27][CH2:28][OH:29])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1.C1(C)C=CC=CC=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].COCCO[AlH2-]OCCOC.[Na+]>O1CCCC1>[CH3:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([CH:26]=[CH:27][CH2:28][OH:29])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 16684438Red-AlHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 22484199HCID 22484199, compound

Product 1

HCID 69116274HCID 69116274, compoundYield 47.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 0.56 g (1.47 mmol) of 3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-yn-1-ol (prepared by Method B) in 6 mL of dry tetrahydrofuran at 0° C. was added 0.73 mL of a 65% weight toluene solution of sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al, 2.35 mmol) in 1 mL of THF. The reaction was stirred at room temperature for 3 hours. Upon recooling to 0° C. an additional 0.73 mL of the Red-Al solution in 1 mL of THF was added. After stirring for 1 hour at room temperature, the mixture was quenched with the dropwise addition of 10% aqueous potassium carbonate and extracted with ethyl acetate. The organic extracts were dried over sodium sulfate, filtered and evaporated to give 650 mg. Chromatography on 90 g silica gel, eluting with 96:4:0.1 chloroform/methanol/concentrated ammonium hydroxide afforded 268 mg of the title compound. 1H NMR (d6 DMSO): δ 9.79 (s, 1), 8.57 (m, 2), 8.35 (m, 2), 8.01 (m, 1), 7.80 (m, 3), 7.41 (m, 1), 7.29 (m, 1), 7.07 (d, J=8.7 Hz, 1), 6.77 (d, J=16.2 Hz, 1), 6.67 (m, 1), 5.04 (t, J=5.6 Hz, 1), 4.23 (m, 2), 2.23 (s, 3).

Workup

  1. customUpon recooling to 0° C.
  2. additionwas added
  3. stirringAfter stirring for 1 hour at room temperature
  4. customthe mixture was quenched with the dropwise addition of 10% aqueous potassium carbonate
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto give 650 mg
  10. washChromatography on 90 g silica gel, eluting with 96:4:0.1 chloroform/methanol/concentrated ammonium hydroxide

Sources & evidence

ORD record
ord-d6e13d74dd9947ff89e37f3958c9fa26
Source dataset
uspto-grants-2008_02
Patent number
US07332493B2

Reaction notes

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