Acetic Acid → 9-ethyl-2-(methylamino)-9H-pyrido[2,3-b]indole-3-carboxamide

HRID 1158757Notes

Reaction equation

HRID 1158757 reaction equation
[NH2:1][C:2]1[C:3]([C:17]([NH2:19])=[O:18])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([CH2:14][CH3:15])[C:6]=2[N:16]=1.C=O.[C:22](O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH2:14]([N:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:5]2[CH:4]=[C:3]([C:17]([NH2:19])=[O:18])[C:2]([NH:1][CH3:22])=[N:16][C:6]1=2)[CH3:15]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 152709832-amino-9-ethyl-9H-pyrido[2,3-b]indole-3-carboxamide

Product 1

HCID 249009329-ethyl-2-(methylamino)-9H-pyrido[2,3-b]indole-3-carboxamideYield 66.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-amino-9-ethyl-9H-pyrido[2,3-b]indole-3-carboxamide (1, 36 mg, 0.141 mmol), formaldehyde (37 wt % in water, 0.011 mL, 0.155 mmol) and acetic acid (0.0084 mL, 0.148 mmol) in methanol (2.6 mL) were stirred at room temperature for 1 h then sodium cyanoborohydride (13 mg, 0.212 mmol) was added. The reaction stirred at room temperature for 16 h, then was quenched with aqueous saturated sodium bicarbonate (2.6 mL). The resulting mixture was diluted with ethyl acetate (100 mL), washed with water (2×50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and then concentrated in vacuo. The residue was adsorbed onto silica gel using methanol and purified by silica gel chromatography (5-10% methanol in methylene chloride gradient) to afford the title compound (48, 25 mg, 66%). NH4OAc standard conditions. DAD Retention time =7.84 min. M+H=269. 1H NMR (300 MHz, CDCl3): δ 8.60 (br s, 1H), 8.19 (s, 1H), 7.79 (d, J=7.9 Hz, 1H), 7.36-7.32 (m, 2H), 7.21-7.17 (m, 1H), 5.65 (br s, 2H), 4.38 (q, J=7.3 Hz, 2H), 3.12 (s, 3H), 1.42 (t, J=7.3 Hz, 3H).

Workup

  1. customwas quenched with aqueous saturated sodium bicarbonate (2.6 mL)
  2. additionThe resulting mixture was diluted with ethyl acetate (100 mL)
  3. washwashed with water (2×50 mL) and brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography (5-10% methanol in methylene chloride gradient)

Sources & evidence

ORD record
ord-70efe32087f946b39afd74b9310ed447
Source dataset
uspto-grants-2010_10
Patent number
US07812018B2

Reaction notes

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