Acetic Acid → tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidine-1-carboxylate tert-Butyl trans(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidine-1-carboxylate

HRID 43869

Reaktionsgleichung

Reaktionsgleichung von HRID 43869
[CH2:1]([CH:3]([NH2:6])[CH2:4][CH3:5])[CH3:2].[Cl:7][C:8]1[N:9]=[C:10]([C:15]([NH:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][C:19]2=O)=[O:16])[NH:11][C:12]=1[CH2:13][CH3:14].C([BH3-])#N.[Na+].C(O)(=O)C>O1CCCC1.CO>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][C@@H:18]([NH:17][C:15]([C:10]2[NH:11][C:12]([CH2:13][CH3:14])=[C:8]([Cl:7])[N:9]=2)=[O:16])[C@H:19]([NH:6][CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[CH2:20]1)=[O:25])([CH3:30])([CH3:29])[CH3:28].[Cl:7][C:8]1[N:9]=[C:10]([C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][C@H:19]2[NH:6][CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])=[O:16])[NH:11][C:12]=1[CH2:13][CH3:14]

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 120193-PentanamineHCID 5003444Sodium cyanoborohydrideHCID 68406285tert-Butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate

Produkt 1

HCID 131730875tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidine-1-carboxylate tert-Butyl trans(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidine-1-carboxylateAusbeute 7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

1-Ethylpropylamine (124 μL, 1.06 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) (197 mg, 0.531 mmol) in tetrahydrofuran (4 mL), and the mixture was heated under reflux at 50° C. for four hours. Methanol (3 mL) was added to the reaction solution. Sodium cyanoborohydride (100 mg, 1.59 mmol) and acetic acid (304 μL, 5.31 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 49 mg of the cis isomer of the title compound (21%) as a pale yellow oily substance and 16 mg of the trans isomer of the title compound (7%) as a pale yellow oily substance.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-dbdc0d7a76f44455be56168b47f4b090
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536197B2

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