Binap, (A+-)- → 1-(1-{4-[7-(1-Ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-phenyl}-piperidin-4-yl)-ethanone

HRID 2189291Notes

Reaction equation

HRID 2189291 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12]N(C(=O)C)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:17][C:18](C)([O-:20])[CH3:19].[Na+].Cl[C:24]1[N:25]=[CH:26][C:27]2[CH:32]=[CH:31][N:30]([CH:33]([CH2:36][CH3:37])[CH2:34][CH3:35])[C:28]=2[N:29]=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>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]>[CH2:34]([CH:33]([N:30]1[C:28]2[N:29]=[C:24]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([N:8]4[CH2:9][CH2:10][CH:17]([C:18](=[O:20])[CH3:19])[CH2:12][CH2:13]4)=[CH:6][CH:7]=3)[N:25]=[CH:26][C:27]=2[CH:32]=[CH:31]1)[CH2:36][CH3:37])[CH3:35]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 7362691-[4-(4-Aminophenyl)piperazin-1-yl]ethan-1-oneHCID 23676156Sodium t-butoxideHCID 580159322-Chloro-7-(pentan-3-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 689530131-(1-{4-[7-(1-Ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-phenyl}-piperidin-4-yl)-ethanoneYield 80.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a mixture of 1-[4-(4-amino-phenyl)-piperazin-1-yl]-ethanone (70.5 mg, 0.32 mmol) and sodium tert-butoxide (38.4 mg, 0.4 mmol) in 1,4-dioxane (0.3 mL) are added a solution of 2-chloro-7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine (60 mg, 0.26 mmol) in 1,4-dioxane (0.6 mL), Pd2(dba)3 (12.2 mg, 0.013 mmol) and BINAP (16.6 mg, 0.026 mmol). The mixture is degassed, and heated at 100° C. for 3 h. The mixture is cooled to room temperature, diluted with EtOAc, and filtered through a pad of Celite. The filtrate is concentrated under reduced pressure. The crude product is purified by preparative HPLC to give 84.9 mg of 1-(1-{4-[7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-phenyl}-piperidin-4-yl)-ethanone as a pale white solid.

Workup

  1. customThe mixture is degassed
  2. temperatureThe mixture is cooled to room temperature
  3. additiondiluted with EtOAc
  4. filtrationfiltered through a pad of Celite
  5. concentrationThe filtrate is concentrated under reduced pressure
  6. customThe crude product is purified by preparative HPLC

Sources & evidence

ORD record
ord-640d2b812b354c4d807d5ecca3595381
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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