HCID 68411356, compound → (+/-)-4-(3-Aminopyridin-4-yl)-2-(tert-butoxycarbonylamino)-6-methylcyclohexyl acetate

HRID 879162Notes

Reaction equation

HRID 879162 reaction equation
[C:1]([O:4][CH:5]1[CH:10]([CH3:11])[CH2:9][C:8]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=2[N+:18]([O-])=O)=[CH:7][CH:6]1[NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])(=[O:3])[CH3:2]>CO.CCOC(C)=O.[Pd]>[C:1]([O:4][CH:5]1[CH:10]([CH3:11])[CH2:9][CH:8]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=2[NH2:18])[CH2:7][CH:6]1[NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])(=[O:3])[CH3:2]

Participants

5

Reactant 1

HCID 68411356HCID 68411356, compound

Product 1

HCID 68411339(+/-)-4-(3-Aminopyridin-4-yl)-2-(tert-butoxycarbonylamino)-6-methylcyclohexyl acetateYield 59%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a degassed solution of (+/−)-2-(tert-butoxycarbonylamino)-6-methyl-4-(3-nitropyridin-4-yl)cyclohex-3-enyl acetate (1.0 equiv.) in MeOH and EtOAc (1:1, 0.1 M) was added 10% Pd/C (0.1 equiv.) and the reaction was stirred at room temperature under a hydrogen balloon for 3 days. Upon completion, the solution was filtered through a pad of Celite, the pad was washed with ethyl acetate and the filtrate was concentrated. The crude material contained about 10% of the undesired isomer. The crude was dissolved in ethyl acetate (˜20%) and hexanes and heated until all dissolved. The solution was allowed to sit at room temperature for 2 days. The precipitate was then collected to give (+/−)-4-(3-aminopyridin-4-yl)-2-(tert-butoxycarbonylamino)-6-methylcyclohexyl acetate as the pure product in 59% yield. LC/MS=364.3 (M+H), Rt=0.63 min. The racemic material was resolved using an AD-H chiral column (20% i-PrOH/80% n-heptanes, 20 mL/min flow rate) to (1S,2S,4S,6R)-4-(3-aminopyridin-4-yl)-2-((tert-butoxycarbonyl)amino)-6-methylcyclohexyl acetate (peak#1, Rt=3.76 min on AD-H chiral analytical column, 20% i-PrOH/80% n-heptanes, 1 mL/min) and (1R,2R,4R,6S)-4-(3-aminopyridin-4-yl)-2-((tert-butoxycarbonyl)amino)-6-methylcyclohexyl acetate (peak#2, Rt=6.79 min on AD-H chiral analytical column, 20% i-PrOH/80% n-heptanes, 1 mL/min).

Workup

  1. filtrationUpon completion, the solution was filtered through a pad of Celite
  2. washthe pad was washed with ethyl acetate
  3. concentrationthe filtrate was concentrated
  4. dissolutionThe crude was dissolved in ethyl acetate (˜20%)
  5. temperaturehexanes and heated until all dissolved
  6. waitto sit at room temperature for 2 days
  7. customThe precipitate was then collected

Sources & evidence

ORD record
ord-ee9dc82c86a74c8ca157701847e4f384
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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