Pyridine → HCID 44542671, compound

HRID 1675233Notes

Reaction equation

HRID 1675233 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:35][CH2:36][CH2:37][O:38][CH3:39])=[C:24]([NH:27][C:28]([C@@H:30]4[CH2:34][CH2:33][CH2:32][NH:31]4)=[O:29])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[C:40](O)(=[O:43])[CH:41]=[CH2:42].N1C=CC=CC=1.Cl.CN(C)CCCN=C=NCC>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:35][CH2:36][CH2:37][O:38][CH3:39])=[C:24]([NH:27][C:28]([C@@H:30]4[CH2:34][CH2:33][CH2:32][N:31]4[C:40](=[O:43])[CH:41]=[CH2:42])=[O:29])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6581Acrylic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11656852HCID 11656852, compound

Product 1

HCID 44542671HCID 44542671, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

302 mg of (2S)-pyrrolidine-2-carboxylic acid {4-[3-chloro-4-(pyridin-2-ylmethoxy)-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 0.15 ml of acrylic acid, 0.18 ml of pyridine and 0.53 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 (31 mg, 9%).

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-0357d800051c48dfbe7d21049fc10882
Source dataset
uspto-grants-2011_08
Patent number
US08003658B2

Reaction notes

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