N-[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]-3-nitroquinolin-4-amine → N4-[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]quinoline-3,4-diamine

HRID 44726Notes

Reaction equation

HRID 44726 reaction equation
[Si:1]([O:8][C:9]1([CH2:15][CH2:16][CH2:17][NH:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[CH:21][C:20]=2[N+:29]([O-])=O)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>[Pt].C(OCC)(=O)C>[Si:1]([O:8][C:9]1([CH2:15][CH2:16][CH2:17][NH:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[CH:21][C:20]=2[NH2:29])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 57515401N-[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]-3-nitroquinolin-4-amine

Product 1

HCID 86616864N4-[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]quinoline-3,4-diamine

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]-3-nitroquinolin-4-amine (1.40 g, 3.16 mmol) and 5% platinum on carbon (0.14 g) in ethyl acetate (15 mL) was hydrogenated at 30 psi (2.1×105 Pa) for 2 h on a Parr apparatus. The reaction mixture was filtered through CELITE filter agent, which was rinsed with ethyl acetate afterwards, and the filtrate was concentrated to give N4-[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]quinoline-3,4-diamine as an orange colored gum. The gum was dissolved in dichloromethane (15 mL) and the solution was cooled to 0° C. Ethoxyacetyl chloride (0.350 mL, 3.48 mmol) was added dropwise over 2 min. The reaction was allowed to stir at 0° C. for 1 h, then was concentrated in vacuo to yield N-(4-{[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]amino}quinolin-3-yl)-2-ethoxyacetamide hydrochloride as a yellow solid. The yellow solid was dissolved in ethanol (12 mL) and 2 M NaOH (2.4 mL, 4.8 mmol) was added. The reaction was heated at 60° C. for 1 h. The reaction was cooled to rt and the solvent was removed in vacuo. The residue was partitioned between dichloromethane (50 mL) and water (30 mL), and 1 M HCl was added to the mixture until the pH=7-8. The aqueous layer was extracted with dichloromethane (2×15 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated to afford 1-[3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinoline as a brown oil (1.57 g, 96%) that contained some dichloromethane.

Workup

  1. filtrationThe reaction mixture was filtered through CELITE
  2. filtrationfilter agent, which
  3. washwas rinsed with ethyl acetate afterwards
  4. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-d6d73c8e10c04725a50ea1b346030a6f
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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