Hydrochloric Acid → Ethyl 3-((6-(4-(1-((tert-butoxycarbonyl)amino)cyclobutyl)phenyl)-3-nitro-5-phenylpyridin-2-yl)amino)propanoate

HRID 1509255Notes

Reaction equation

HRID 1509255 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:22][C:21]([N+:30]([O-:32])=[O:31])=[C:20](Cl)[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[NH2:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46].Cl>CCO.O>[C:1]([O:5][C:6]([NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]([NH:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:21]([N+:30]([O-:32])=[O:31])=[CH:22][C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)=[O:34])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 419889Ethyl 3-aminopropanoateHCID 87326920Tert-butyl(1-(4-(6-chloro-5-nitro-3-phenylpyridin-2-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 67255294Ethyl 3-((6-(4-(1-((tert-butoxycarbonyl)amino)cyclobutyl)phenyl)-3-nitro-5-phenylpyridin-2-yl)amino)propanoate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl(1-(4-(6-chloro-5-nitro-3-phenylpyridin-2-yl)phenyl)cyclobutyl)carbamate (1.03 g, 2.14 mmol) in EtOH (8 ml) was added triethylamine (1.49 ml, 10.72 mmol) and ethyl 3-aminopropanoate.HCl (1.65 g, 10.72 mmol) under nitrogen. The resulting mixture was stirred for 1.5 hours at 80° C. under microwave irradiation. Water was added and the mixture was extracted with AcOEt (3×15 ml). The combined organic phases were dried over Na2SO4 and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 30% EtOAc in cyclohexane) to give the title compound (1.2 g, quantitative). 1H NMR (500 MHz, CDCl3): 8.50 (1H, s), 8.38 (1H, s), 7.32 (2H, d), 7.23-7.18 (5H, m), 7.09-7.07 (2H, m), 5.00 (1H, br s), 4.12 (2H, q), 3.98 (2H, q), 2.71-2.68 (2H, t), 2.52-2.20 (4H, m), 2.00-1.95 (1H, m), 1.79-1.65 (1H, m), 1.40-1.10 (9H, br), 1.20 (3H, t).

Workup

  1. extractionthe mixture was extracted with AcOEt (3×15 ml)
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. concentrationconcentrated to dryness under reduced pressure
  4. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-f35cba3f499947e8a33d7c6f32a9b69e
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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