Potassium Carbonate → 4-[4-Chloro-1-(4-methoxy-benzyl)-1H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester

HRID 1295666Notes

Reaction equation

HRID 1295666 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:14]3[N:15]=[CH:16][N:17]=[C:18]([Cl:19])[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34]Cl)=[CH:32][CH:31]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC(=O)CC>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:6]=[CH:7][C:8]([C:11]2[N:20]=[C:14]3[N:15]([CH2:34][C:33]4[CH:36]=[CH:37][C:30]([O:29][CH3:28])=[CH:31][CH:32]=4)[CH:16]=[N:17][C:18]([Cl:19])=[C:13]3[CH:12]=2)=[CH:9][CH:10]=1)[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 232826964-(4-Chloro-7H-pyrrolo[2,3-D]pyrimidin-6-YL)benzoic acid ethyl ester

Product 1

HCID 865953384-[4-Chloro-1-(4-methoxy-benzyl)-1H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 3.0 g (10 mMol) of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-benzoic acid ethyl ester (WO 97/02266), 2.4 g (17 mMol) of K2CO3, 0.32 g (1 mMol) of tetrabutyl-ammoniumbromide and 2.0 ml (15 mMol) of 4-methoxy-benzylchloride in 25 ml of 2-butanone is stirred for 18 h at 80° C. Then the suspension is filtered, the residue washed with 2-butanone and discarded. The filtrate is diluted with EtOAc and water, the aqueous layer separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated after adding 13 g of SiO2. The resulting powder is put on top of a chromatography column (SiO2) and then eluted with hexane/EtOAc 2:1. 4-[4-Chloro-7-(4-methoxy-benzyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester [TLC (hexane/EtOAc 2:1) Rf=0.40; MS-ES+: (M+H)+=422] is eluated first, followed by the title compound; TLC (hexane/EtOAc 2:1) Rf=0.23; MS-ES+: (M+H)+=422.

Workup

  1. filtrationThen the suspension is filtered
  2. washthe residue washed with 2-butanone
  3. additionThe filtrate is diluted with EtOAc and water
  4. customthe aqueous layer separated off
  5. extractionextracted twice with EtOAc
  6. washThe organic layers are washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. additionafter adding 13 g of SiO2
  10. washeluted with hexane/EtOAc 2:1

Sources & evidence

ORD record
ord-dcdc56bd5d414c0ebb3c0334bc1580d0
Source dataset
uspto-grants-2007_07
Patent number
US07244729B2

Reaction notes

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