1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-N-((5-fluoro-3-methylbenzo[b]thiophen-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamide

HRID 2097151Notes

Reaction equation

HRID 2097151 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]([CH2:10][NH:11][CH3:12])=[C:8]([CH3:9])[C:4]=2[CH:3]=1.[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>[F:1][C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]([CH2:10][N:11]([CH3:12])[C:28](=[O:30])/[CH:27]=[CH:26]/[C:23]3[CH:24]=[N:25][C:18]4[NH:17][C:16](=[O:15])[CH2:21][O:20][C:19]=4[CH:22]=3)=[C:8]([CH3:9])[C:4]=2[CH:3]=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 59456918[(5-Fluoro-3-methylbenzo[b]thiophen-2-yl)methyl]methylamine

Product 1

HCID 16660979(E)-N-((5-fluoro-3-methylbenzo[b]thiophen-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamideYield 13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (5-fluoro-3-methylbenzo[b]thiophen-2-yl)-N-methyl methanamine (200 mg, 0.96 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 (185 mg, 0.87 mmol), 1-hydroxybenzotriazole (133 mg, 0.96 mmol), diisopropylethylamine (454 uL, 2.61 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (192 mg, 0.96 mmol). The mixture was stirred at room temperature overnight, cooled in an ice bath and water added with rapid stirring. The product was extracted with ethyl acetate (3×10 mL), dried with sodium sulfate, filtered and concentrated. The crude product was purified using preparative HPLC to give the title compound (45 mg, 13%): 1H NMR (400 MHz, DMSO-d6) δ 11.42 (bs, 1H), 8.19 (s, 1H), 7.89-7.87 (m, 2H), 7.55-7.51 (m, 2H), 7.22-7.18 (m, 2H), 5.12-4.87 (2s, 2H, rotamers), 4.68 (s, 2H), 3.54 (s, 3H), 2.39 (s, 3H). MS (ESI) m/e 412 (C21H18FN3O3S+H)+.

Workup

  1. temperaturecooled in an ice bath
  2. extractionThe product was extracted with ethyl acetate (3×10 mL)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-f7a9808308ae4d899d933a1d8056c773
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

Loading…