Acetonitrile → {3-[3-(2-methoxy-pyridin-3-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone

HRID 272014Notes

Reaction equation

HRID 272014 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[N:4]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:3]=1.F[C:34](F)(F)[C:35]1C=C(B(O)O)[CH:38]=[CH:39][CH:40]=1.[C:46](=[O:49])([O-])[O-].[Na+].[Na+].C(#[N:54])C>[Br-].[Na+].C(OCC)(=O)C>[CH3:46][O:49][C:34]1[C:35]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([C:11]4[CH:12]=[C:13]([C:17]([N:19]5[CH2:24][CH2:23][O:22][CH2:21][CH2:20]5)=[O:18])[CH:14]=[CH:15][CH:16]=4)[CH:9]=3)[N:4]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:3]=2)=[CH:40][CH:39]=[CH:38][N:54]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 59836119(3-(3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)(morpholino)methanone

Product 1

HCID 68617336{3-[3-(2-methoxy-pyridin-3-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanoneYield 116%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 253881Sodium BromideSolvent

Procedure

A mixture of {3-[3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone (33 mg, 66% pure, 38 μmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichlormethane adduct (5 mg, 6 μmol) and 3-trifluoromethylphenylboronic acid (14 mg, 92 μmol) in acetonitrile (2 mL) and 2 M solution of sodium carbonate (1 mL) was irradiated in a Personal Chemistry Optimizer at 175° C. for 20 min. The crude reaction mixture was diluted with saturated aqueous solution of sodium bromide (1 mL) and ethyl acetate (4 mL) and the organic phase separated, adsorbed onto silica and purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford {3-[3-(2-methoxy-pyridin-3-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone (24 mg, 116% yield) as an off-white residue. MS: m/z 568 [MNa+], 546 [MH+], 428 [MH+-(Me3Si(CH2)2O)]

Workup

  1. customwas irradiated in a Personal Chemistry Optimizer at 175° C. for 20 min
  2. customThe crude reaction mixture
  3. customthe organic phase separated
  4. custompurified by flash silica gel chromatography

Sources & evidence

ORD record
ord-9101c01ed25b4a5bbdc9e77c1f389909
Source dataset
uspto-grants-2008_11
Patent number
US07452993B2

Reaction notes

Loading…