Formaldehyde → N-{4-(4-bromo-2-fluoro-phenylamino)-7-[2-(2-dimethylamino-propionylamino)-ethoxy]-quinazolin-6-yl}-acrylamide

HRID 81455Notes

Reaction equation

HRID 81455 reaction equation
N[CH:2]([CH3:33])[C:3]([NH:5][CH2:6][CH2:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][C:21]=3[F:27])=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[NH:28][C:29](=[O:32])[CH:30]=[CH2:31])=[O:4].[CH2:34]=O.[C:36]([BH3-])#[N:37].[Na+]>C1COCC1.CO>[Br:26][C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([O:8][CH2:7][CH2:6][NH:5][C:3](=[O:4])[CH:2]([N:37]([CH3:36])[CH3:34])[CH3:33])=[C:10]([NH:28][C:29](=[O:32])[CH:30]=[CH2:31])[CH:11]=3)[N:16]=[CH:15][N:14]=2)=[C:21]([F:27])[CH:22]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 16678543N-[7-[2-(2-amino-propionylamino)-ethoxy]-4-(4-bromo-2-fluoro-phenylamino)-quinazolin-6-yl]-acrylamide

Product 1

HCID 16679451N-{4-(4-bromo-2-fluoro-phenylamino)-7-[2-(2-dimethylamino-propionylamino)-ethoxy]-quinazolin-6-yl}-acrylamideYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-[7-[2-(2-amino-propionylamino)-ethoxy]-4-(4-bromo-2-fluoro-phenylamino)-quinazolin-6-yl]-acrylamide (30 mg, 0.06 mmol) and 37 weight % of formaldehyde (9 μl, 0.12 mmol) were diluted with THF (1 ml) and methanol (1 ml), and stirred at room temperature for 10 min. Sodium cyanoborohydride (11 mg, 0.17 mmol) was added thereto, and the solution was stirred for 4 hours. The resulting solution was distilled under a reduced pressure to remove the solvent, saturated sodium bicarbonate aqueous solution (20 ml) was added thereto, and extracted with chloroform (20 ml) twice. The separated organic layer was dried over magnesium sulfate, filtered and distilled under a reduced pressure, and resulting impure residue was subjected to column chromatography to obtain the title compound 23 mg (yield: 73%).

Workup

  1. stirringthe solution was stirred for 4 hours
  2. distillationThe resulting solution was distilled under a reduced pressure
  3. customto remove the solvent, saturated sodium bicarbonate aqueous solution (20 ml)
  4. additionwas added
  5. extractionextracted with chloroform (20 ml) twice
  6. dry with materialThe separated organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. distillationdistilled under a reduced pressure
  9. customresulting impure residue

Sources & evidence

ORD record
ord-997f1c4d2fe946ed96883f8c9eb2b539
Source dataset
uspto-grants-2014_09
Patent number
US08846699B2

Reaction notes

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