Diethyl cyanophosphonate → (4-Ethyl-piperazin-1-yl]-[4-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl]-methanone

HRID 133056Notes

Reaction equation

HRID 133056 reaction equation
[Li+].[F:2][C:3]1[C:11]([O:12][C:13]2[C:14]3[CH:21]=[C:20]([C:22]4[CH:30]=[CH:29][C:25]([C:26]([O-:28])=O)=[CH:24][CH:23]=4)[NH:19][C:15]=3[N:16]=[CH:17][N:18]=2)=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([CH3:31])[NH:7]2.[CH2:32]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)[CH3:33].C(OP(C#N)(=O)OCC)C>CN(C=O)C.CCOC(C)=O>[CH2:32]([N:34]1[CH2:39][CH2:38][N:37]([C:26]([C:25]2[CH:24]=[CH:23][C:22]([C:20]3[NH:19][C:15]4[N:16]=[CH:17][N:18]=[C:13]([O:12][C:11]5[C:3]([F:2])=[C:4]6[C:8](=[CH:9][CH:10]=5)[NH:7][C:6]([CH3:31])=[CH:5]6)[C:14]=4[CH:21]=3)=[CH:30][CH:29]=2)=[O:28])[CH2:36][CH2:35]1)[CH3:33]

Participants

6

Reactant 3

HCID 76257Diethyl cyanophosphonateHCID 791961-EthylpiperazineHCID 691806194-[4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid lithium salt

Product 1

HCID 10207082(4-Ethyl-piperazin-1-yl]-[4-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl]-methanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 340 mg (0.83 mMol) 4-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid lithium salt in 5 ml of DMF under N2-atmosphere, 0.38 ml (3 mMol) of N-ethylpiperazine and 0.31 ml (95%; 2 mMol) of diethyl-cyanphosphonate are added at 0° C. After 60 min, the suspension is diluted with EtOAc and washed with saturated NaHCO3-solution, water and brine. The aqueous layers are reextracted twice with EtOAc, the organic layers dried (Na2SO4) and concentrated after adding SiO2. The resulting powder is put on top of a chromatography column (SiO2) and the title compound eluted with EtOAc/methanol/NH3conc. 80:20:1; HPLC (conditions see Examples 67-78) tR=10.4 min; MS-ES+: (M+H)+=499.

Workup

  1. washwashed with saturated NaHCO3-solution, water and brine
  2. dry with materialthe organic layers dried (Na2SO4)
  3. concentrationconcentrated
  4. additionafter adding SiO2
  5. washthe title compound eluted with EtOAc/methanol/NH3conc

Sources & evidence

ORD record
ord-28dc93308f8d4a3d9fe14cc087215647
Source dataset
uspto-grants-2008_06
Patent number
US07390805B2

Reaction notes

Loading…