Pyridine → N-(4-(3-Chloro-4-(pyridin-2-YL-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-YL-oxy)quinolin-6-YL)acrylamide

HRID 714584Notes

Reaction equation

HRID 714584 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH:13]1[CH2:17][CH2:16][O:15][CH2:14]1)[N:8]=[CH:7][C:6]([C:18]#[N:19])=[C:5]2[NH:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[C:23]([Cl:35])[CH:22]=1.N1C=CC=CC=1.[CH2:42]1C[O:45][CH2:44][CH2:43]1.C(Cl)(=O)C=C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[Cl:35][C:23]1[CH:22]=[C:21]([NH:20][C:5]2[C:4]3[C:9](=[CH:10][C:11]([O:12][CH:13]4[CH2:17][CH2:16][O:15][CH2:14]4)=[C:2]([NH:1][C:44](=[O:45])[CH:43]=[CH2:42])[CH:3]=3)[N:8]=[CH:7][C:6]=2[C:18]#[N:19])[CH:26]=[CH:25][C:24]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8028TetrahydrofuranHCID 13140Acryloyl chlorideHCID 866945566-Amino-4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-7-(tetrahydrofuran-3-yl-oxy)quinolin-3-carbonitrile

Product 1

HCID 56592385N-(4-(3-Chloro-4-(pyridin-2-YL-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-YL-oxy)quinolin-6-YL)acrylamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a reaction flask were added 6-amino-4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-7-(tetrahydrofuran-3-yl-oxy)quinolin-3-carbonitrile (100 mg, 0.205 mmol), pyridine (0.3 ml), DMAP (20 mg) and THF (10 ml). The mixture was cooled to the temperature of 0° C. To the mixture was added acryloyl chloride (20 mg, 0.22 mmol). The resultant mixture was stirred for 30 min at the temperature of 0° C. Then the mixture was warmed to the room temperature and stirred for 5 hr. After the reaction finished, the resultant mixture was filtered and the filtrate was rotary-evaporated to dryness to give a solid. The solid was dissolved in ethyl acetate. The solution was washed with saturated sodium carbonate once, acetic acid solutioni (10%) once and saturated saline once, successively. The resulting solution was dried over anhydrous magnesium sulfate, filtered and rotary-evaporated to dryness to give a crude prodcut. The product was purified with thin layer chromatography.

Workup

  1. temperatureThen the mixture was warmed to the room temperature
  2. filtrationthe resultant mixture was filtered
  3. customthe filtrate was rotary-evaporated to dryness
  4. customto give a solid
  5. washThe solution was washed with saturated sodium carbonate once
  6. dry with materialThe resulting solution was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customrotary-evaporated to dryness
  9. customto give a crude prodcut
  10. customThe product was purified with thin layer chromatography

Sources & evidence

ORD record
ord-727c39ddabbf4061af379289bcec7509
Source dataset
uspto-grants-2015_11
Patent number
US09187458B2

Reaction notes

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