Pyridine → HCID 67334302, compound

HRID 1675235Notes

Reaction equation

HRID 1675235 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:36][CH2:37][CH2:38][O:39][CH3:40])=[C:25]([NH:28][C:29]([C@@H:31]4[CH2:35][CH2:34][CH2:33][NH:32]4)=[O:30])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[C:41](O)(=[O:44])[CH:42]=[CH2:43].N1C=CC=CC=1.Cl.CN(C)CCCN=C=NCC>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:36][CH2:37][CH2:38][O:39][CH3:40])=[C:25]([NH:28][C:29]([C@@H:31]4[CH2:35][CH2:34][CH2:33][N:32]4[C:41](=[O:44])[CH:42]=[CH2:43])=[O:30])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6581Acrylic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67336498HCID 67336498, compound

Product 1

HCID 67334302HCID 67334302, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

288 mg of (2S)-pyrrolidine-2-carboxylic acid {4-[3-chloro-4-(3-fluoro-benzyloxy)-phenylamino]-7-(2-methoxyethoxy)-quinazolin-6-yl}-amide as a starting material was dissolved in 10 ml of THF, and cooled to 0° C. The solution was reacted with 0.07 ml of acrylic acid, 0.17 ml of pyridine and 0.29 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride at 0° C. for 30 mins and at room temperature for 2 hours. The reacted solution was extracted with a mixture of chloroform and isopropanol after adding water, washed with saturated saline solution, dried over anhydrous sodium sulfate, filtered and distilled under a reduced pressure, and the resulting residue was subjected to column chromatography (eluent-ethylacetate:methanol=30:1) to obtain the title compound (52 mg, 17%).

Workup

  1. extractionThe reacted solution was extracted with a mixture of chloroform and isopropanol
  2. additionafter adding water
  3. washwashed with saturated saline solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. distillationdistilled under a reduced pressure

Sources & evidence

ORD record
ord-87d7513585584fd9a81e473aaa9b3d56
Source dataset
uspto-grants-2011_08
Patent number
US08003658B2

Reaction notes

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