1,2-Dichloroethane → (E)-3-(6-Amino-pyridin-3-yl)-N-(3-chloro-benzofuran-2-ylmethyl)-N-methyl-acrylamide hydrochloride

HRID 2097115Notes

Reaction equation

HRID 2097115 reaction equation
C(Cl)C[Cl:3].[NH2:5][C:6]1[N:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]([OH:16])=O)=[CH:8][CH:7]=1.C1C=CC2N(O)N=NC=2C=1.[Cl:27][C:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[O:30][C:29]=1[CH2:37][NH:38][CH3:39].C(N(C(C)C)C(C)C)C>CN(C=O)C.O>[ClH:3].[NH2:5][C:6]1[N:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([N:38]([CH2:37][C:29]2[O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:28]=2[Cl:27])[CH3:39])=[O:16])=[CH:8][CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 534008323-(6-Aminopyridin-3-yl)prop-2-enoic acidHCID 59277587(3-Chloro-benzofuran-2-ylmethyl)methylamine

Product 1

HCID 16660477(E)-3-(6-Amino-pyridin-3-yl)-N-(3-chloro-benzofuran-2-ylmethyl)-N-methyl-acrylamide hydrochlorideYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

EDC (0.21 g, 1.08 mmol) was added to a suspension of 3-(6-amino-pyridin-3-yl)-acrylic acid (148 mg, 0.9 mmol), HOBt (134 mg, 1 mmol), (3-chloro-benzofuran-2-ylmethyl)methylamine (194 mg, 0.99 mmol), and (i-Pr)2EtN (0.75 mL, 4.46 mmol) in DMF (16 mL). The mixture was stirred overnight at room temperature then cooled to 0° C. and diluted with H2O (32 mL) with rapid stirring. The resulting precipitate was collected by filtration, washed with H2O (32 mL) and dried under high vacuum. The residue was re-solvated in methylene chloride (5 mL) and a solution of 2M HCl in ether (2 mL) was added to precipitate the hydrogen chloride salt. The precipitate was collected by filtration and dried to give the title compound (295 mg, 89%) as a white solid and as a mixture of amide rotomers. 1H NMR (300 MHz, DMSO-d6) δ 8.40-8.42 (m, 3H), 7.57-7.65 (m, 2H), 7.38-7.46 (m, 3H), 6.98-7.03 (m, 1H), 4.86-5.05 (rotamers, 2s, 2H), 3.20 (s, 3H); MS (ESI) m/e 342 (C18H16ClN3O2+H)+.

Workup

  1. temperaturethen cooled to 0° C.
  2. filtrationThe resulting precipitate was collected by filtration
  3. washwashed with H2O (32 mL)
  4. customdried under high vacuum
  5. additiona solution of 2M HCl in ether (2 mL) was added
  6. customto precipitate the hydrogen chloride salt
  7. filtrationThe precipitate was collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-4d1ae1ff37c6455c8b09712df7fce2af
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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