Methoxyacetic Acid → N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-2-methoxyacetamide

HRID 222286Notes

Reaction equation

HRID 222286 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:16]=[CH:15][C:9]3=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=[C:8]3[C:7](=[O:17])[C:6]=2[CH:18]=1.[CH3:19][O:20][CH2:21][C:22](O)=[O:23].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>ClCCl.C(#N)C.O.C(OCC)(=O)C>[Cl:14][C:12]1[CH:13]=[C:8]2[C:7](=[O:17])[C:6]3[CH:18]=[C:2]([NH:1][C:22](=[O:23])[CH2:21][O:20][CH3:19])[CH:3]=[CH:4][C:5]=3[CH:16]=[CH:15][C:9]2=[N:10][CH:11]=1

Participants

9

Reactant 4

HCID 12251Methoxyacetic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 159808217-amino-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

Product 1

HCID 57722750N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-2-methoxyacetamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

7-amino-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (0.70 g, 2.7 mmol) was dissolved in 20 mL of dry dichloromethane and 5 mL of dry acetonitrile. Methoxyacetic acid (0.32 mL, 4.1 mmol), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) (0.79 g, 4.1 mmol) and 1-hydroxybenzotriazole hydrate (HOBt) (0.55 g, 4.1 mmol) were added and the solution was stirred at ambient temperature. After 12 hours, the reaction solution was poured into 300 mL of ethyl acetate and 100 mL of water. The organic layer was separated and washed with 100 mL of brine. The organic layer was separated, dried with magnesium sulfate, filtered, concentrated and purified by flash column chromatography (0-100% ethyl acetate/hexanes gradient) to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 10.29 (s, 1H); 8.94 (d, 1H); 8.58 (d, 1H); 8.46 (d, 1H); 8.10 (dd, 1H); 7.77 (d, 1H); 7.40 (d, 1H); 7.20 (d, 1H); 4.04 (s, 2H); 3.36 (s, 3H). LRMS (APCI) calculated for C17H14C1N2O3 [M+H]+, 329.1; found 329.1.

Workup

  1. customThe organic layer was separated
  2. washwashed with 100 mL of brine
  3. customThe organic layer was separated
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash column chromatography (0-100% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-c31ee1e13be543cbbabc8e3028d3e2f9
Source dataset
uspto-grants-2012_06
Patent number
US08207186B2

Reaction notes

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