Pyridine → (1R)-N-(1-{4-[3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-(2-methoxy-ethoxy)-quinazolin-6-ylcarbamoyl}-ethyl)-acrylamide

HRID 1675231Notes

Reaction equation

HRID 1675231 reaction equation
[C:1]([OH:5])(=O)[CH:2]=[CH2:3].N1C=CC=CC=1.Cl.CN(C)CCCN=C=NCC.[NH2:24][CH:25]([CH3:60])[C:26]([NH:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][C:38]=1[O:39][CH2:40][CH2:41][O:42][CH3:43])[N:35]=[CH:34][N:33]=[C:32]2[NH:44][C:45]1[CH:50]=[CH:49][C:48]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=2)=[C:47]([Cl:59])[CH:46]=1)=[O:27]>C1COCC1>[Cl:59][C:47]1[CH:46]=[C:45]([NH:44][C:32]2[C:31]3[C:36](=[CH:37][C:38]([O:39][CH2:40][CH2:41][O:42][CH3:43])=[C:29]([NH:28][C:26]([C@H:25]([NH:24][C:1](=[O:5])[CH:2]=[CH2:3])[CH3:60])=[O:27])[CH:30]=3)[N:35]=[CH:34][N:33]=2)[CH:50]=[CH:49][C:48]=1[O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6581Acrylic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67333476HCID 67333476, compound

Product 1

HCID 67335505(1R)-N-(1-{4-[3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-(2-methoxy-ethoxy)-quinazolin-6-ylcarbamoyl}-ethyl)-acrylamideYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

75 μl of acrylic acid was dissolved in 4 ml of THF, and cooled to 0° C. 180 μl of pyridine and 520 ml of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added thereto, the resulting solution was reacted with 284 mg of 2-amino-N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-(2-methoxy-ethoxy)-quinazolin-6-yl]-propionamide dissolved in 4 ml of THF as a starting material for 30 mins, and then stirred for 3 hours while heating to room temperature. The reacted solution was washed with saturated sodium bicarbonate solution, extracted with a mixture of chloroform and methanol, dried over sodium sulfate, filtered and distilled under a reduced pressure, and the resulting residue was subjected to column chromatography (eluent-chloroform:methanol=15:1) to obtain the title compound (87 mg, 28%).

Workup

  1. temperaturewhile heating to room temperature
  2. washThe reacted solution was washed with saturated sodium bicarbonate solution
  3. extractionextracted with a mixture of chloroform and methanol
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. distillationdistilled under a reduced pressure

Sources & evidence

ORD record
ord-d346f87d600c4515ad48790a96e5f36c
Source dataset
uspto-grants-2011_08
Patent number
US08003658B2

Reaction notes

Loading…