Chloride → 5-(2,3-difluorophenyl)-2-oxocycloheptyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate

HRID 1666119Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1666119
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:15][CH2:14][C:13](=[O:16])[CH:12]([OH:17])[CH2:11][CH2:10]1.Cl[C:19](OC1C=CC([N+]([O-])=O)=CC=1)=[O:20].[Cl-].[NH:32]1[CH2:37][CH2:36][CH:35]([N:38]2[C:46]3[C:41](=[N:42][CH:43]=[CH:44][CH:45]=3)[NH:40][C:39]2=[O:47])[CH2:34][CH2:33]1.CCN(C(C)C)C(C)C>C1COCC1.CN(C1C=CN=CC=1)C.O>[O:47]=[C:39]1[NH:40][C:41]2=[N:42][CH:43]=[CH:44][CH:45]=[C:46]2[N:38]1[CH:35]1[CH2:34][CH2:33][N:32]([C:19]([O:17][CH:12]2[CH2:11][CH2:10][CH:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])[CH2:15][CH2:14][C:13]2=[O:16])=[O:20])[CH2:37][CH2:36]1

Komponenten

9

Edukt 5

HCID 312ChlorideHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 22293182Bms-973013HCID 579114815-(2,3-Difluorophenyl)-2-hydroxycycloheptanone

Produkt 1

HCID 461747765-(2,3-difluorophenyl)-2-oxocycloheptyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

In an oven-dried 50 mL round-bottomed flask (t=g) was added 5-(2,3-difluorophenyl)-2-hydroxycycloheptanone (22 mg, 0.092 mmol) and 4-Nitrophenyl chloroformate (20.30 mg, 0.101 mmol) in THF (3 mL) to give a colorless solution. DMAP (15.66 mg, 0.128 mmol) was added, and the mixture was stirred at room temperature for 3 hours. TLC showed a new less polar spot (more polar than the chloride) but mainly starting material. Allowed reaction to stir overnight for 24 hours. To the above reaction mixture was added 1-(piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (53.6 mg, 0.184 mmol), followed by Hunig's Base (0.040 mL, 0.230 mmol). The resulted mixture was stirred at room temperature overnight. LCMS showed two close small peaks which has the MW of 484. 22 h: It was diluted with water and extracted with EtOAc. The organic layer was washed 3 times with water, brine, dried with Na2SO4 and concentrated to a tan oil. FCC up to 8% MeOH/CH2Cl2 afforded the desired product as mixture of two diasteromers: 11.7 mg (26%). LCMS: M+H=485.

Aufarbeitung

  1. customto give a colorless solution
  2. customAllowed reaction
  3. stirringto stir overnight for 24 hours
  4. stirringThe resulted mixture was stirred at room temperature overnight
  5. customclose small peaks which
  6. extractionextracted with EtOAc
  7. washThe organic layer was washed 3 times with water, brine
  8. dry with materialdried with Na2SO4
  9. concentrationconcentrated to a tan oil

Quellen und Nachweise

ORD-Eintrag
ord-13127e5d41bb4b2c8be53c565141c3c4
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044043B2

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