Triethylamine → 7-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide

HRID 2410682Notes

Reaction equation

HRID 2410682 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:7]3[N:15]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=4)[CH:13]=[C:12]([C:24]([OH:26])=O)[C:8]=3[NH:9][C:10]=2[CH:11]=1.[Cl-].[NH4+].Cl.C[N:31](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CO.C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:7]3[N:15]=[C:14]([C:16]4[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=4)[CH:13]=[C:12]([C:24]([NH2:31])=[O:26])[C:8]=3[NH:9][C:10]=2[CH:11]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 666050157-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylic acid

Product 1

HCID 666049587-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamideYield 61%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 7-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylic acid (60 mg, 0.17 mmol), ammonium chloride (15 mg, 0.28 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodimide hydrochloride (43 mg, 0.22 mmol), and 1-hydroxybenzotriazole hydrate (30 mg, 0.22 mmol) in a vial was flushed with nitrogen and dimethylformamide (0.5 mL) followed by triethylamine (38 μL, 0.28 mmol) were added. After stirring overnight, the reaction was diluted with methanol and the product was isolated by preparative HPLC (100×30 mm Luna C18 column, gradient elution starting with A:B=10:90 and ending with A:B=70:30 [A=10 mM NH4OAc in 5% aqueous acetonitrile; B=10 mM NH4OAc in 95% aqueous acetonitrile] over 20 min) This gave 7-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (36 mg, 57% yield) as a yellow solid. MS (ESI) m/z 348.0 (M+H). 1H NMR (MeOD) δ ppm 8.27 (1H, d, J=8.85 Hz), 8.09 (1H, s), 8.04 (2H, d, J=8.85 Hz), 7.18 (1H, d, J=2.14 Hz), 7.09 (2H, d, J=8.55 Hz), 6.92 (1H, dd, J=8.55, 2.14 Hz), 3.95 (3H, s), 3.90 (3H, s).

Workup

  1. customwas flushed with nitrogen and dimethylformamide (0.5 mL)
  2. additionwere added
  3. customthe product was isolated by preparative HPLC (
  4. wash100×30 mm Luna C18 column, gradient elution

Sources & evidence

ORD record
ord-649161d15aa94d21bb9f3e2a11f93a8e
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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