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 1099151Notes

Reaction equation

HRID 1099151 reaction equation
[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

Participants

9

Reactant 5

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

Product 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

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-f435db563eac4b07a8250f0acb02a44f
Source dataset
uspto-grants-2012_03
Patent number
US08143403B2

Reaction notes

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