(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 2097117Notes

Reaction equation

HRID 2097117 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-9151ddd6ce2443d8bcd7bc950acba698
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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