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

HRID 2189273Notes

Reaction equation

HRID 2189273 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]([O-:21])(C)[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:21])[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 NaOtBu (38.4 mg, 0.4 mmol) in 1,4-dioxane (0.3 mL) is 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) and a suspension of 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 hours. Then the mixture is cooled down to room temperature, diluted with EtOAc, and filtered through celite. The filtrate is concentrated under reduced pressure. The crude product is purified prep-HPLC to give 84.9 mg of the title compound as pale white solid.

Workup

  1. customThe mixture is degassed
  2. temperatureThen the mixture is cooled down to room temperature
  3. additiondiluted with EtOAc
  4. filtrationfiltered through celite
  5. concentrationThe filtrate is concentrated under reduced pressure
  6. customThe crude product is purified prep-HPLC

Sources & evidence

ORD record
ord-c3c1c5dfc64347488b6e1e3f4d953ab8
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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