1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-N-((3-ethylbenzofuran-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamide

HRID 2097150Notes

Reaction equation

HRID 2097150 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].[O:15]=[C:16]1[CH2:21][O:20][C:19]2[CH:22]=[C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=O)[CH:24]=[N:25][C:18]=2[NH:17]1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.CN(C)CCCN=C=NCC>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:28](=[O:30])/[CH:27]=[CH:26]/[C:23]1[CH:24]=[N:25][C:18]2[NH:17][C:16](=[O:15])[CH2:21][O:20][C:19]=2[CH:22]=1)[CH3:2]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57742058(E)-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acidHCID 59277558(3-Ethyl-benzofuran-2-ylmethyl)methylamine

Product 1

HCID 16660978(E)-N-((3-ethylbenzofuran-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamideYield 53.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-ethylbenzofuran-2-yl)-N-methylmethanamine (115 mg, 0.6 mmol) in DMF (5 mL) were added in sequential order (E)-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid (140 mg, 0.54 mmol), 1-hydroxybenzotriazole (84 mg, 0.6 mmol), diisopropylethylamine (282 uL, 1.62 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (120 mg, 0.6 mmol). The mixture was stirred at room temperature overnight, cooled in an ice bath and water added with rapid stirring. The product precipitated and was filtered, triturated with ether and dried to yield the title compound as a white solid (113 mg, 52%): 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 8.19 (s, 1H), 7.88 (d, J=6.4 Hz, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.51-7.49 (m, 2H), 7.29-7.25 (m, 3H), 4.99-4.79 (rotamers, 2s, 2H), 4.68 (s, 2H), 3.39 (s, 3H), 2.79-2.73 (m, 2H), 1.23-1.20 (m, 3H); MS (ESI) m/e 392 (C22H21N3O4+H)+.

Workup

  1. temperaturecooled in an ice bath
  2. customThe product precipitated
  3. filtrationwas filtered
  4. customtriturated with ether
  5. customdried

Sources & evidence

ORD record
ord-c6796e9bdc6849d59023ebef1e8afa77
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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