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

HRID 1362369Notes

Reaction equation

HRID 1362369 reaction equation
Cl.[O:2]=[C:3]1[NH:9][C:8]2[N:10]=[CH:11][C:12]([CH:14]=[CH:15][C:16]([OH:18])=O)=[CH:13][C:7]=2[CH2:6][NH:5][CH2:4]1.[Cl:19][C:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[O:22][C:21]=1[CH2:29][NH:30][CH3:31]>>[ClH:19].[Cl:19][C:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[O:22][C:21]=1[CH2:29][N:30]([CH3:31])[C:16](=[O:18])/[CH:15]=[CH:14]/[C:12]1[CH:11]=[N:10][C:8]2[NH:9][C:3](=[O:2])[CH2:4][NH:5][CH2:6][C:7]=2[CH:13]=1

Participants

3

Reactant 2

HCID 59277587(3-Chloro-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 16660480(E)-N-(3-Chloro-benzofuran-2-ylmethyl)-N-methyl-3-(2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylamide hydrochlorideYield 34.1%

Procedure

According to the method of example 43d, 3-(2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid hydrochloride (152 mg, 0.5 mmol) and (3-chloro-benzofuran-2-ylmethyl)methylamine (108 mg, 0.55 mmol) were coupled to yield crude product which was triturated with methanol and ether several times and dried. 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 (42 mg, 19%) as a white solid and as a mixture of amide rotomers. 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.45 (s, 1H), 8.01 (s, 1H), 7.38-7.68 (m, 6H), 4.88-5.08 (rotamers, 2s, 2H), 3.90 (s, 2H), 3.63 (s, 2H), 3.31 (s, 3H); MS (ESI) m/e 411 (C21H19ClN4O3+H)+.

Workup

  1. customto yield crude product which
  2. customwas triturated with methanol and ether several times
  3. customdried
  4. additiona solution of 2M HCl in ether (2 mL) was added
  5. customto precipitate the hydrogen chloride salt
  6. filtrationThe precipitate was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-b915441ab06c4885bb3fa7707fdd96e0
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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