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

HRID 2097143Notes

Reaction equation

HRID 2097143 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].[O:14]=[C:15]1[CH2:20][O:19][C:18]2[CH:21]=[C:22](/[CH:25]=[CH:26]/[C:27]([OH:29])=O)[CH:23]=[N:24][C:17]=2[NH:16]1.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:17]2[NH:16][C:15](=[O:14])[CH2:20][O:19][C:18]=2[CH:21]=1

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 59277587(3-Chloro-benzofuran-2-ylmethyl)methylamine

Product 1

HCID 16660975(E)-N-((3-chlorobenzofuran-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamideYield 30.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-chlorobenzofuran-2-yl)-N-methylmethanamine (100 mg, 0.51 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 (107 mg, 0.46 mmol), 1-hydroxybenzotriazole (71 mg, 0.51 mmol), diisopropylethylamine (243 uL, 1.39 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (102 mg, 0.51 mmol). The mixture was stirred at room temperature overnight, cooled in an ice bath and water was added with rapid stirring. The product precipitated and was filtered, triturated with ether and dried to yield title compound as a white solid (55 mg, 30%): 1H NMR (400 MHz, CDCl3) δ 9.21 (s, 1H), 8.12-8.19 (m, 1H), 7.28-7.6 (m, 7H), 4.81-4.95 (rotamers, 2s, 2H), 4.714 (s, 2H); 3.21 (s, 3H); MS (ESI) m/e 398 (C20H16ClN3O4+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-e73159a3e01d4cdf875f419a20913649
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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