2-Pyrrolidone → HCID 57562605, compound

HRID 1725485Notes

Reaction equation

HRID 1725485 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:24])[C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:17]=3[F:23])[CH2:11][CH2:10]2)[N:5]=[C:4]([NH:25][C:26]2[S:27][CH:28]=[CH:29][N:30]=2)[CH:3]=1.[NH:31]1[CH2:35][CH2:34][CH2:33][C:32]1=[O:36].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.C(OCC)(=O)C>[Cl:22][C:18]1[C:17]([F:23])=[C:16]([CH:21]=[CH:20][CH:19]=1)[C:15]([N:12]1[CH2:13][CH2:14][N:9]([CH2:8][C:6]2[CH:7]=[C:2]([N:31]3[CH2:35][CH2:34][CH2:33][C:32]3=[O:36])[CH:3]=[C:4]([NH:25][C:26]3[S:27][CH:28]=[CH:29][N:30]=3)[N:5]=2)[CH2:10][CH2:11]1)=[O:24]

Participants

7

Reactant 4

HCID 120252-PyrrolidoneHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57562613HCID 57562613, compound

Product 1

HCID 57562605HCID 57562605, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 25.5 mg of 4-bromo-6-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-N-thiazol-2-ylpyridin-2-amine obtained in Example 81 in 1 mL of 1,4-dioxane was added 0.011 mL of pyrrolidin-2-one, 32 mg of potassium phosphate, 8.7 mg of 9,9-dimethyl4,5-bis(diphenylphosphino)xanthene and 7.8 mg of tris(dibenzylideneacetone)dipalladium(0)-chloroform complex, successively. The reaction solution was stirred at 100° C. for 3 hours. The reaction solution was cooled, diluted with ethyl acetate, washed with water, and then dried over anhydrous magnesium sulfate. The solvent was concentrated in vacuo and the resulting residue was purified by a reversed phase medium pressure liquid chromatography [ODS-AS-360-CC (manufactured by YMC company), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]. The obtained fraction was diluted with ethyl acetate, washed with saturated sodium bicarbonate, and then dried over anhydrous magnesium sulfate. The solvent was concentrated in vacuo to give the title compound.

Workup

  1. temperatureThe reaction solution was cooled
  2. washwashed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationThe solvent was concentrated in vacuo
  5. customthe resulting residue was purified by a reversed phase medium pressure liquid chromatography [ODS-AS-360-CC (manufactured by YMC company), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]
  6. additionThe obtained fraction was diluted with ethyl acetate
  7. washwashed with saturated sodium bicarbonate
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationThe solvent was concentrated in vacuo

Sources & evidence

ORD record
ord-2670479f307748efb76470bf5a57f6d1
Source dataset
uspto-grants-2009_02
Patent number
US07491720B2

Reaction notes

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