Binap, (A+-)- → 1-{2-[4-(4-Acetyl-piperazin-1-yl)-phenylamino]-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-ethanone

HRID 2189332Notes

Reaction equation

HRID 2189332 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH3:11])=[C:9]([C:12](=[O:14])[CH3:13])[N:8]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:6]=2[N:7]=1.[NH2:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][N:30]([C:33](=[O:35])[CH3:34])[CH2:29][CH2:28]2)=[CH:23][CH:22]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>O1CCOCC1.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].O>[C:33]([N:30]1[CH2:29][CH2:28][N:27]([C:24]2[CH:25]=[CH:26][C:21]([NH:20][C:2]3[N:3]=[CH:4][C:5]4[C:10]([CH3:11])=[C:9]([C:12](=[O:14])[CH3:13])[N:8]([CH:15]5[CH2:19][CH2:18][CH2:17][CH2:16]5)[C:6]=4[N:7]=3)=[CH:22][CH:23]=2)[CH2:32][CH2:31]1)(=[O:35])[CH3:34]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 7362691-[4-(4-Aminophenyl)piperazin-1-yl]ethan-1-oneHCID 23676156Sodium t-butoxideHCID 866373511-(2-Chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-ethanone

Product 1

HCID 690791801-{2-[4-(4-Acetyl-piperazin-1-yl)-phenylamino]-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-ethanoneYield 24.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 1-(2-Chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-ethanone (40 mg, 0.144 mmol), 1-[4-(4-Amino-phenyl)-piperazin-1-yl]-ethanone (37.9 mg, 0.172 mmol), Pd2(dba)3 (6.7 mg, 0.007 mmol), BINAP (9.15 mg, 0.014 mmol) and NaOtBu (20.7 mg, 0.216 mmol) in 1,4-dioxane (4 mL) is degassed and back-filled with nitrogen three times. The reaction mixture is heated to 80° C. for 2 hours. After cooling to room temperature water is added and the reaction mixture is extracted with ethyl acetate three times. The organic layers are combined, washed with brine and dried over anhydrous sodium sulfate. The solvent is evaporated and the crude material is purified by preparative HPLC to provide 1-{2-[4-(4-Acetyl-piperazin-1-yl)-phenylamino]-7-cyclopentyl-5methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-ethanone (16 mg, 24%). [M+H]+=461.13.

Workup

  1. additionback-filled with nitrogen three times
  2. additionis added
  3. extractionthe reaction mixture is extracted with ethyl acetate three times
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent is evaporated
  7. customthe crude material is purified by preparative HPLC

Sources & evidence

ORD record
ord-00066a99eb55469aa23d42407dd4a2a1
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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