Hydrochloric Acid → HCID 22181289, compound

HRID 1796526Notes

Reaction equation

HRID 1796526 reaction equation
CO[C:3](=O)[NH:4][C:5]1[CH:6]=[C:7]2[N:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH3:23])=[CH:17][CH:16]=3)[N:11]([CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:8]2=[N:9][CH:10]=1.Cl.[H-].[H-].[H-].[H-].[Li+].[Al+3]>ClCCl.C(OCC)C>[CH:25]1([CH2:24][N:11]2[C:8]3=[N:9][CH:10]=[C:5]([NH:4][CH3:3])[CH:6]=[C:7]3[N:13]=[C:12]2[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH3:23])=[CH:17][CH:16]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 21226445Aluminium lithium hydrideHCID 69595812HCID 69595812, compound

Product 1

HCID 22181289HCID 22181289, compoundYield 90.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of [3-(cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-3H-imidazo[4,5-b]pyridin-6-yl]-carbamic acid methyl ester (550 mg, 1.46 mmol) in dichloromethane (20 mL) at room temperature was added 1 M HCl in diethyl ether solution (3 mL). The mixture was stirred for 10 minutes and concentrated in vacuo. The residue was taken up into THE (5 mL) and diethyl ether (30 mL) and cooled to 0° C. LAH (137 mg, 3.61 mmol) was added to the solution. The mixture was stirred overnight. The reaction was then cooled to −78° C. and quenched with MeOH (3.20 mL) and water (3.20 mL). Na2SO4 was added to the mixture which was allowed to slowly warm up to room temperature. The mixture was filtered over Celite and concentrated in vacuo. The residue was purified using silica gel flash chromatography ([3.5% MeOH+0.5% NH4OH aq] in CH2Cl2) to provide 445 mg of the title compound 3-(cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-N-methyl-3H-imidazo[4,5-b]pyridin-6-amine (90.6% yield from [3-(cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-3H-imidazo[4,5-b]pyridin-6-yl]-carbamic acid methyl ester). 1H-NMR (400 MHz, CDCl3): δ 0.35 (m, 2H), 0.46 (m, 2H), 1.11 (m, 1H), 1.39 (t, J=7.0 Hz, 3H), 2.90 (s, 3H), 3.98 (m, 4H), 4.25 (s, 2H), 6.83 (d, J=8.8 Hz, 2H), 7.15 (d, J=8.8 Hz, 2H), 7.23 (d, J=2.5 Hz, 1H), 7.83 (d, J=2.5 Hz, 1H). MS (ESI) (M+H)+: 337.

Workup

  1. concentrationconcentrated in vacuo
  2. stirringThe mixture was stirred overnight
  3. temperatureThe reaction was then cooled to −78° C.
  4. customquenched with MeOH (3.20 mL) and water (3.20 mL)
  5. additionNa2SO4 was added to the mixture which
  6. temperatureto slowly warm up to room temperature
  7. filtrationThe mixture was filtered over Celite
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified

Sources & evidence

ORD record
ord-2109c0181856489996f89da55485a5ff
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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