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

HRID 2097139Notes

Reaction equation

HRID 2097139 reaction equation
[Cl:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH2:11][NH:12][CH3:13].[CH3:14][C:15]1([CH3:31])[O:20][C:19]2[CH:21]=[C:22]([CH:25]=[CH:26][C:27]([OH:29])=O)[CH:23]=[N:24][C:18]=2[NH:17][C:16]1=[O:30].ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.CN(C)CCCN=C=NCC>CN(C=O)C.O>[Cl:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH2:11][N:12]([CH3:13])[C:27](=[O:29])/[CH:26]=[CH:25]/[C:22]1[CH:23]=[N:24][C:18]2[NH:17][C:16](=[O:30])[C:15]([CH3:14])([CH3:31])[O:20][C:19]=2[CH:21]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59277587(3-Chloro-benzofuran-2-ylmethyl)methylamineHCID 669676363-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-acrylic acid

Product 1

HCID 16660818(E)-N-(3-Chloro-benzofuran-2-ylmethyl)-3-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-acrylamideYield 73.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-chloro-benzofuran-2-ylmethyl)-methyl-amine (151 mg, 0.77 mmol) in DMF (5 mL) were added in sequential order 3-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-acrylic acid (174 mg, 0.7 mmol), 1-hydroxybenzotriazole (107 mg, 0.77 mmol), diisopropylethylamine (366 uL, 2.1 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (154 mg, 0.77 mmol). The mixture was stirred at room temperature overnight, cooled in an ice bath and treated with water under rapid stirring. The precipitated product was filtered and dried, triturated with diethyl ether to yield the title compound (218 mg, 73%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 8.21 (s, 1H), 7.96 (s, 1H), 7.53-7.67 (m, 3H), 7.40-7.44 (m, 3H), 4.89-5.11 (m, 2H), 2.97-3.23 (m, 3H), 1.46 (s, 6H); MS (ESI) m/e 426 (C22H20ClN3O4+H)+.

Workup

  1. temperaturecooled in an ice bath
  2. filtrationThe precipitated product was filtered
  3. customdried
  4. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-43c4014c564645a2b6c73eba72a16cc3
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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