Sodium Bicarbonate → N-((1H-indol-7-yl)methyl)-N-methyl-5,6,7,8-tetrahydroquinolin-8-amine

HRID 628675Notes

Reaction equation

HRID 628675 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[CH:10]=O)[CH:3]=[CH:2]1.[CH3:12][NH:13][CH:14]1[C:23]2[N:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:17][CH2:16][CH2:15]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.C(O)(=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[CH2:10][N:13]([CH3:12])[CH:14]2[C:23]3[N:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH2:17][CH2:16][CH2:15]2)[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 2734629Indole-7-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58985336N-methyl-5,6,7,8-tetrahydroquinolin-8-amine

Product 1

HCID 59176454N-((1H-indol-7-yl)methyl)-N-methyl-5,6,7,8-tetrahydroquinolin-8-amineYield 76%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
65 °C

Procedure

A solution of indole-7-carboxaldehyde (0.48 g, 3.36 mmol) in 1,2-dichloroethane (10 mL) was treated with N-methyl-5,6,7,8-tetrahydroquinolin-8-amine, 5, (0.60 g, 3.70 mmol), sodium triacetoxyborohydride (1.07 g, 5.05 mmol) and a catalytic amount of acetic acid (2 drops). The resulting mixture was warmed to 65° C. and stirred for 2 h. The reaction mixture was cooled to room temperature and a saturated aqueous solution of sodium bicarbonate was added. The product was extracted with dichloromethane. The combined organic layers were dried over potassium carbonate, filtered and concentrated in vacuo. The product was purified by silica gel chromatography (0-5% methanol/CH2Cl2) to afford 0.75 g (76% yield) of the desired product: 1H NMR (400 MHz, CDCl3) δ 12.69 (bs, 1H), 8.61 (d, J=4.4 Hz, 1H), 7.85-7.81 (m, 1H), 7.68-7.65 (m, 1H), 7.59 (d, J=7.2 Hz, 1H), 7.44-7.38 (m, 2H), 7.12 (dd, J=4.4, 7.2 Hz, 1H), 7.03-6.96 (m, 2H), 6.55 (t, J=2.0 Hz, 1H), 4.22-4.17 (m, 1H), 4.00 (d, J=13.4 Hz, 1H), 3.84 (t, J=6.8 Hz, 1H), 3.73 (d, J=13.4 Hz, 1H), 3.42 (t, J=6.8 Hz, 1H), 2.92-2.72 (m, 2H), 2.28 (s, 3H), 2.14-2.04 (m, 1H), 2.00-1.88 (m, 1H), 1.85-1.70 (m, 1H); ESI+ MS: m/z (rel intensity) 292.1 (90, [M+H]+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe product was extracted with dichloromethane
  3. dry with materialThe combined organic layers were dried over potassium carbonate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe product was purified by silica gel chromatography (0-5% methanol/CH2Cl2)

Sources & evidence

ORD record
ord-45845f8ba04d4c898f59b4efa2dc3240
Source dataset
uspto-grants-2016_04
Patent number
US09314468B2

Reaction notes

Loading…