Acetic Acid → HCID 86648804, compound

HRID 1425334Notes

Reaction equation

HRID 1425334 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C:17]2=O)=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12].C([BH3-])#N.[Na+].C(O)(=O)C>O1CCCC1>[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][C@@H:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:18][C@H:17]2[NH:4][CH:1]2[CH2:3][CH2:2]2)=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 69828Cyclopropylamine2×HCID 5003444Sodium cyanoborohydrideHCID 68406285tert-Butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate

Product 1

HCID 86648804HCID 86648804, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Cyclopropylamine (249 μL, 3.59 mmol) was added to a solution of tert-butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate obtained in Example (201c) (190 mg, 0.512 mmol) in tetrahydrofuran (6 mL), and the mixture was heated under reflux at 50° C. for four hours. The reaction solution was concentrated under reduced pressure, and then tetrahydrofuran (3 mL) and methanol (3 mL) were added. Cyclopropylamine (71.0 μL, 0.102 mmol), sodium cyanoborohydride (97.0 mg, 1.54 mmol) and acetic acid (293 μL, 5.12 mmol) were added, and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure. Saturated aqueous sodium bicarbonate solution was added to the residue, followed by extraction with ethyl acetate. The resulting organic layer was washed with brine, and dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography and preparative TLC (eluent: chloroform:methanol=10:1 v/v) to obtain 34 mg of the cis isomer of the title compound (16%) as a pale yellow oily substance and 32 mg of the trans isomer of the title compound (15%) as a pale yellow oily substance.

Workup

  1. temperaturethe mixture was heated
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additiontetrahydrofuran (3 mL) and methanol (3 mL) were added
  4. concentrationThe reaction solution was concentrated under reduced pressure
  5. additionSaturated aqueous sodium bicarbonate solution was added to the residue
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe resulting organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customthe insoluble matter was separated by filtration
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe resulting residue was purified by silica gel column chromatography and preparative TLC (eluent: chloroform:methanol=10:1 v/v)

Sources & evidence

ORD record
ord-cc020b734e2944de9bcf262fa1797f68
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

Loading…