1-Acetyl-4-(4-fluorobenzoyl)piperidine → HCID 118006290, compound

HRID 926608Notes

Reaction equation

HRID 926608 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([O:17][CH:18]([F:20])[F:19])[C:11]([CH2:21][C:22]1[CH:23]=[N:24][CH:25]=[N:26][CH:27]=1)=[C:10]2[O:28][CH:29]([F:31])[F:30].[F:32][C:33]1[CH:49]=[CH:48][C:36]([C:37]([CH:39]2[CH2:44][CH2:43][N:42]([C:45](=[O:47])[CH3:46])[CH2:41][CH2:40]2)=[O:38])=[CH:35][CH:34]=1>C1COCC1>[F:19][CH:18]([F:20])[O:17][C:12]1[C:11]([CH2:21][C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=2)=[C:10]([O:28][CH:29]([F:31])[F:30])[C:9]2[C:14](=[CH:15][CH:16]=[C:7]([C:37]([C:36]3[CH:35]=[CH:34][C:33]([F:32])=[CH:49][CH:48]=3)([OH:38])[CH:39]3[CH2:40][CH2:41][N:42]([C:45](=[O:47])[CH3:46])[CH2:43][CH2:44]3)[CH:8]=2)[N:13]=1

Participants

5

Reactant 3

HCID 1172571-Acetyl-4-(4-fluorobenzoyl)piperidine2×HCID 118006214HCID 118006214, compound2×HCID 178418339Butyllithium

Product 1

HCID 118006290HCID 118006290, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-BuLi (1.6 M in THF, 0.26 mL, 0.41 mmol) was added dropwise over a 1 minute period to a mixture of 6-bromo-2,4-bis(difluoromethoxy)-3-(pyrimidin-5-ylmethyl)quinoline (0.16 g, 0.37 mmol, Intermediate 50) and 1-(4-(4-fluorobenzoyl)piperidin-1-yl)ethanone (0.10 g, 0.41 mmol, Intermediate 44) in dry THF (3.8 mL) at −78° C. Stirring was continued at −78° C. for 10 minutes. The reaction mixture was then placed in an ice bath and stirred at 0° C. for 1 hour. The reaction was then quenched with aqueous NH4Cl, diluted with water and extracted with EtOAc (2×). The EtOAc extracts were dried over Na2SO4, filtered, evaporated in vacuo and purified by FCC (0-10% MeOH in DCM, gradient) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 9.00-9.19 (m, 1H), 8.61-8.79 (m, 2H), 8.05-8.22 (m, 1H), 7.69-7.93 (m, 3H), 7.37-7.56 (m, 2H), 6.93-7.13 (m, 2H), 6.36-6.89 (m, 1H), 4.59-4.83 (m, 1H), 4.20 (s, 2H), 3.67-3.97 (m, 1H), 2.95-3.23 (m, 1H), 2.43-2.83 (m, 2H), 2.04 (s, 3H), 1.61-1.79 (m, 1H), 1.30-1.51 (m, 3H); MS (ESI) 603 [M+H]+.

Workup

  1. customThe reaction mixture was then placed in an ice bath
  2. stirringstirred at 0° C. for 1 hour
  3. customThe reaction was then quenched with aqueous NH4Cl
  4. additiondiluted with water
  5. extractionextracted with EtOAc (2×)
  6. dry with materialThe EtOAc extracts were dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. custompurified by FCC (0-10% MeOH in DCM, gradient)

Sources & evidence

ORD record
ord-039b0bd61fc84373a87f46cee5b87c21
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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