Potassium Carbonate → 2-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetonitrile

HRID 1525870Notes

Reaction equation

HRID 1525870 reaction equation
Cl.[CH:2]1([N:5]2[CH2:10][C:9]3([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[O:8][CH2:7][C:6]2=[O:16])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH:24]([C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:42]=[C:41]3[C:36]([CH:37]=[CH:38][CH:39]=[N:40]3)=[CH:35][CH:34]=2)=[CH:29][CH:28]=1)[C:25]#[N:26]>CN(C)C=O.O>[CH:2]1([N:5]2[CH2:10][C:9]3([CH2:11][CH2:12][N:13]([CH:24]([C:27]4[CH:32]=[CH:31][C:30]([C:33]5[CH:42]=[C:41]6[C:36]([CH:37]=[CH:38][CH:39]=[N:40]6)=[CH:35][CH:34]=5)=[CH:29][CH:28]=4)[C:25]#[N:26])[CH2:14][CH2:15]3)[O:8][CH2:7][C:6]2=[O:16])[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 69083351HCID 69083351, compoundHCID 867254212-Bromo-2-(4-(quinolin-7-yl)phenyl)acetonitrile

Product 1

HCID 712708342-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride (0.101 mmol) in N,N-dimethylformamide (0.5 mL) was treated with potassium carbonate (0.209 mmol) and 2-bromo-2-(4-(quinolin-7-yl)phenyl)acetonitrile (0.070 mmol). The reaction was stirred overnight at room temperature, at which point it was diluted with water (50 mL) and was extracted with three times with dichloromethane. The aqueous layer was further diluted with brine (25 mL) and was extracted twice with tetrahydrofuran. The organic layers were combined and dried over sodium sulfate, filtered and concentrated in vacuo. The resulting crude material was purified by silica gel chromatography (0-9% methanol/dichloromethane). The fractions containing the desired product were combined, concentrated in vacuo, and lyophilized from water to afford the title compound a pale yellow solid (15%). MS(ES)+ m/e 453.2 [M+H]+.

Workup

  1. extractionwas extracted with three times with dichloromethane
  2. additionThe aqueous layer was further diluted with brine (25 mL)
  3. extractionwas extracted twice with tetrahydrofuran
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by silica gel chromatography (0-9% methanol/dichloromethane)
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d77dd4aecfe54113a0841d774f4d8e28
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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