Pyrrolidine → HCID 53374177, compound

HRID 869697Notes

Reaction equation

HRID 869697 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:5]2[N:15]=[C:16]([C:18]3[C:27]([CH3:28])=[N:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)[CH:17]=[C:4]2[N:3]=1.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:28][C:27]1[C:18]([C:16]2[CH:17]=[C:4]3[N:3]=[C:2]([N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:7]=[C:6]([O:8][CH:9]4[CH2:14][CH2:13][O:12][CH2:11][CH2:10]4)[N:5]3[N:15]=2)=[N:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:26]=1

Participants

8

Reactant 4

HCID 31268PyrrolidineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86674513HCID 86674513, compound

Product 1

HCID 53374177HCID 53374177, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-[5-chloro-7-(tetrahydro-2H-pyran-4-yloxy)pyrazolo[1,5-a]pyrimidin-2-yl]-3-methylquinoxaline (90 mg, 0.227 mmol), pyrrolidine (49 mg, 0.682 mmol), sodium tert-butoxide (33 mg, 0.341 mmol), palladium(II) acetate (52 mg, 0.227 mmol), and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (179 mg, 0.454 mmol) in 1,4-dioxane (4.0 mL) was heated at 100° C. for 40 min. After being cooled to ambient temperature, the reaction mixture was poured into water, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, filtrated and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to 1:9) to give 2-methyl-3-[5-pyrrolidin-1-yl-7-(tetrahydro-2H-pyran-4-yloxy)pyrazolo[1,5-a]pyrimidin-2-yl]quinoxaline. MS (APCI): m/z 431 (M+H).

Workup

  1. temperatureAfter being cooled to ambient temperature
  2. extractionthe mixture was extracted with chloroform
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltrated
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to 1:9)

Sources & evidence

ORD record
ord-2c3d1971293a48d8a59a24103b8e6d39
Source dataset
uspto-grants-2015_03
Patent number
US08969376B2

Reaction notes

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