4-Cyanopiperidine → HCID 58548089, compound

HRID 2207813Notes

Reaction equation

HRID 2207813 reaction equation
Br[C:2]1[C:3]([O:8][CH:9]2[CH2:12][N:11]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[NH:23]1[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25][CH2:24]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][C:13]=1[N:11]1[CH2:12][CH:9]([O:8][C:3]2[C:2]([N:23]3[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25][CH2:24]3)=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:10]1

Participants

7

Reactant 4

HCID 1382234-CyanopiperidineHCID 634876Binap, (A+-)-HCID 58547799HCID 58547799, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 58548089HCID 58548089, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(3-((3-bromopyridin-2-yl)oxy)azetidin-1-yl)quinoline (see PREPARATION P2.9; 177 mg, 0.50 mmol), piperidine-4-carbonitrile (55 mg, 0.50 mmol), Pd2(dba)3 (22 mg, 0.025 mmol), 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (16 mg, 0.025 mmol) and t-BuONa (106 mg, 1.0 mmol) in toluene (10 mL) was stirred at 100° C. for 10 hours. The mixture was left to reach RT and filtered through a pad of CELITE® and the filter cake was washed with CH2Cl2 (30 mL). The combined filtrate was evaporated in vacuo and the residue was purified by flash column chromatography (30% to 50% EtOAc in petroleum ether) and followed by purification by reverse phase HPLC (10% to 80% water/MeCN) to afford 1-(2-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyridin-3-yl)piperidine-4-carbonitrile (80 mg, 0.20 mmol, yield 40%). ESI-MS (M+1): 386 calc. for C23H23N5O 385.

Workup

  1. waitThe mixture was left
  2. customto reach RT
  3. filtrationfiltered through a pad of CELITE®
  4. washthe filter cake was washed with CH2Cl2 (30 mL)
  5. customThe combined filtrate was evaporated in vacuo
  6. customthe residue was purified by flash column chromatography (30% to 50% EtOAc in petroleum ether)
  7. customfollowed by purification by reverse phase HPLC (10% to 80% water/MeCN)

Sources & evidence

ORD record
ord-8681c97eb06c4e218a74949bbdfa8d51
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

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