1,2-Dichloroethane → (E)-N-(3-ethyl-benzofuran-2-ylmethyl)-N-methyl-3-(2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide

HRID 2097061Notes

Reaction equation

HRID 2097061 reaction equation
[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][C:4]=1[CH2:12][NH:13][CH3:14])[CH3:2].C(N(C(C)C)C(C)C)C.Cl.[O:25]=[C:26]1[NH:32][C:31]2[N:33]=[CH:34][C:35]([CH:37]=[CH:38][C:39]([OH:41])=O)=[CH:36][C:30]=2[CH2:29][NH:28][CH2:27]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.O>[CH2:1]([C:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][C:4]=1[CH2:12][N:13]([CH3:14])[C:39](=[O:41])/[CH:38]=[CH:37]/[C:35]1[CH:34]=[N:33][C:31]2[NH:32][C:26](=[O:25])[CH2:27][NH:28][CH2:29][C:30]=2[CH:36]=1)[CH3:2]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59277558(3-Ethyl-benzofuran-2-ylmethyl)methylamineHCID 669665093-(2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochloride

Product 1

HCID 16659825(E)-N-(3-ethyl-benzofuran-2-ylmethyl)-N-methyl-3-(2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamideYield 37.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (3-ethyl-benzofuran-2-ylmethyl)methylamine (185 mg, 0.979 mmol) and (i-Pr)2EtN (0.427 mL, 2.44 mmol) in DMF (25 mL) was treated successively with 3-(2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochloride (250 mg, 0.816 mmol), HOBt (115 mg, 0.856 mmol), and EDC (316 mg, 2.44 mmol). After stirring overnight at room temperature, the mixture was diluted with water and then extracted with EtOAc (3×). The combined organics were washed with brine and dried, filtered and concentrated in vacuo. Purification by column chromatography (silica gel, CH2Cl2/CH3OH, 40:2 to 35:2) gave the title compound (125 mg, 37%) as a yellow solid: ESI MS m/z 405 (M+H)+.

Workup

  1. extractionextracted with EtOAc (3×)
  2. washThe combined organics were washed with brine
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by column chromatography (silica gel, CH2Cl2/CH3OH, 40:2 to 35:2)

Sources & evidence

ORD record
ord-211320ae8ff247a1b8fbae586d5a31f0
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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