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

HRID 2410683Notes

Reaction equation

HRID 2410683 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.CN.Cl.[CH3:31][N:32](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CO>[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]([NH:32][CH3:31])=[O:26])[C:8]=3[NH:9][C:10]=2[CH:11]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochlorideHCID 666050157-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylic acid

Product 1

HCID 666053317-methoxy-2-(4-methoxyphenyl)-N-methyl-5H-pyrido[3,2-b]indole-4-carboxamideYield 66.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 7-methoxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylic acid (Example 127D) (60 mg, 0.17 mmol), methylamine hydrochloride (19 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) followed by removal of the solvents. This gave 7-methoxy-2-(4-methoxyphenyl)-N-methyl-5H-pyrido[3,2-b]indole-4-carboxamide (41 mg, 63% yield) as a yellow solid. MS (ESI) m/z 362.3 (M+H). 1H NMR (MeOD) δ ppm 8.26 (1H, d, J=8.55 Hz), 8.00-8.04 (2H, m), 7.98 (1H, s), 7.17 (1H, d, J=2.14 Hz), 7.07-7.10 (2H, m), 6.92 (1H, dd, J=8.70, 2.29 Hz), 3.94 (3H, s), 3.89 (3H, s), 3.06 (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
  5. customB=10 mM NH4OAc in 95% aqueous acetonitrile] over 20 min) followed by removal of the solvents

Sources & evidence

ORD record
ord-9a58064c5d3a415895a973627a29e2e9
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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