Acrylic Acid → N-[4-(3-bromoanilino)-3-cyano[1]benzothieno[3,2-b]pyridin-8-yl]acrylamide

HRID 989336Notes

Reaction equation

HRID 989336 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[S:14][C:13]3[C:8](=[N:9][CH:10]=[C:11]([C:23]#[N:24])[C:12]=3[NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Br:22])[CH:17]=3)[C:6]=2[CH:7]=1.Cl.CN(C)CCCN=C=NCC.[C:37](O)(=[O:40])[CH:38]=[CH2:39].C(N(C(C)C)CC)(C)C>CN(C)C=O.O1CCCC1>[Br:22][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[NH:15][C:12]1[C:11]([C:23]#[N:24])=[CH:10][N:9]=[C:8]2[C:6]3[CH:7]=[C:2]([NH:1][C:37](=[O:40])[CH:38]=[CH2:39])[CH:3]=[CH:4][C:5]=3[S:14][C:13]=12

Participants

7

Reactant 4

HCID 6581Acrylic AcidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 102719978-Amino-4-(3-bromoanilino)-[1]benzothieno[3,2-b]pyridine-3-carbonitrile

Product 1

HCID 10297571N-[4-(3-bromoanilino)-3-cyano[1]benzothieno[3,2-b]pyridin-8-yl]acrylamideYield 36.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. solution of 164 mg (0.417 mmol) of 8-amino-4-(3-bromoanilino)-[1]benzothieno[3,2-b]pyridine-3-carbonitrile and 120 mg (0.626 mmol) of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride in 2 mL of dimethylformamide and 2 mL of tetrahydrofuran is added 0.045 mL (0.656 mmol) of acrylic acid followed by 0.110 mL (0.633 mmol) of diisopropylethylamine. The reaction mixture is stirred at room temperature for 4 hours then partitioned between methylene choride and water. The aqueous layer is extracted with additional methylene chloride and the organic layers are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash chromatography, eluting with a gradient of 95:5 methylene chloride/methanol to 9:1 methylene chloride/methanol, to provide 69 mg of N-[4-(3-bromoanilino)-3-cyano[1]benzothieno[3,2-b]pyridin-8-yl]acrylamide as a light tan solid, mp>300° C. dec.

Workup

  1. customthen partitioned between methylene choride and water
  2. extractionThe aqueous layer is extracted with additional methylene chloride
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash chromatography
  7. washeluting with a gradient of 95:5 methylene chloride/methanol to 9:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-057684a760c94d02aa3a5a35f93b6d83
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Reaction notes

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