2-Cyclopenten-1-one → 3-(2-(4-(Pyridin-2-ylamino)phenoxy)pyridin-3-yl)cyclopent-2-enone

HRID 473664Notes

Reaction equation

HRID 473664 reaction equation
Cl.Br[C:3]1[C:4]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)=[CH:12][CH:11]=2)=[N:5][CH:6]=[CH:7][CH:8]=1.CN(C1CCCCC1)C1CCCCC1.[C:37]1(=[O:42])[CH2:41][CH2:40][CH:39]=[CH:38]1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[NH:16][C:13]1[CH:14]=[CH:15][C:10]([O:9][C:4]2[C:3]([C:39]3[CH2:40][CH2:41][C:37](=[O:42])[CH:38]=3)=[CH:8][CH:7]=[CH:6][N:5]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 135882-Cyclopenten-1-oneHCID 24210N-Methyl dicyclohexylamineHCID 67425919N-(4-(3-Bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride

Product 1

HCID 593739783-(2-(4-(Pyridin-2-ylamino)phenoxy)pyridin-3-yl)cyclopent-2-enone

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
23 °C

Procedure

A suspension of N-(4-(3-bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride (600 mg, 1.585 mmol) in Dioxane (4 mL) was treated with n-methyldicyclohexylamine (1.008 mL, 4.75 mmol, 3.0 equiv). The reaction was stirred at 23° C. for 15 min, followed by the addition of 2-cyclopenten-1-one (0.641 mL, 7.92 mmol, 5.0 equiv) and bis(tri-tert-butylphosphine)palladium (0) (81 mg, 0.158 mmol, 0.1 equiv). The reaction vessel was capped, degassed and backfilled with argon, and heated at 105° C. After 6 h, the reaction was cooled to 23° C., diluted with EtOAc (100 mL) and washed with water (75 mL) and brine (75 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluant: 0.5-3% methanol/dichloromethane), affording 3-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)cyclopent-2-enone. MS (ESI, pos. ion) m/z: 344.1 (M+1). IC50 (uM) 0.015.

Workup

  1. customThe reaction vessel was capped
  2. customdegassed
  3. temperatureheated at 105° C
  4. waitAfter 6 h
  5. temperaturethe reaction was cooled to 23° C.
  6. additiondiluted with EtOAc (100 mL)
  7. washwashed with water (75 mL) and brine (75 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel chromatography (eluant: 0.5-3% methanol/dichloromethane)

Sources & evidence

ORD record
ord-0b7724e61c714c77881e81729c1791d6
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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