Cesium carbonate → 2-[4-(4-acetyl-piperazin-1-yl)-phenylamino]-7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester

HRID 2189322Notes

Reaction equation

HRID 2189322 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:17][O:18][C:19]([C:21]1[N:30]([CH:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[C:24]2[N:25]=[C:26](Cl)[N:27]=[CH:28][C:23]=2[CH:22]=1)=[O:20].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[CH3:17][O:18][C:19]([C:21]1[N:30]([CH:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[C:24]2[N:25]=[C:26]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([N:8]4[CH2:9][CH2:10][N:11]([C:14](=[O:16])[CH3:15])[CH2:12][CH2:13]4)=[CH:6][CH:7]=3)[N:27]=[CH:28][C:23]=2[CH:22]=1)=[O:20]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7362691-[4-(4-Aminophenyl)piperazin-1-yl]ethan-1-oneHCID 866373482-chloro-7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester

Product 1

HCID 580159672-[4-(4-acetyl-piperazin-1-yl)-phenylamino]-7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl esterYield 40.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of 1-[4-(4-amino-phenyl)-piperazin-1-yl]-ethanone (12.1 mg, 0.055 mmol) in 1,4-dioxane (0.5 mL) is added a solution of 2-chloro-7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester (13 mg, 0.046 mmol) in 1,4-dioxane (0.6 mL), Pd2(dba)3 (2.2 mg, 0.0023 mmol), Xantphos (2.7 mg, 0.046 mmol) and Cs2CO3 (22.5 mg, 0.069 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 8.6 mg of 2-[4-(4-acetyl-piperazin-1-yl)-phenylamino]-7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester 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-db76ee365ff24bda91c12cb916550977
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

Loading…