Potassium Carbonate → HCID 21064694, compound

HRID 1243800Notes

Reaction equation

HRID 1243800 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([N:15]3[CH2:20][CH2:19][CH:18]([NH:21][CH2:22][CH:23]([C:25]4[CH:30]=[CH:29][C:28](Br)=[CH:27][N:26]=4)[OH:24])[CH2:17][CH2:16]3)=[CH:8][C:9]=2[C:11]([F:14])([F:13])[F:12])[S:4][C:3]=1[C:32]([NH2:34])=[O:33].[CH3:35][S:36]([C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][CH:44]=1)(=[O:38])=[O:37].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([N:15]3[CH2:20][CH2:19][CH:18]([NH:21][CH2:22][CH:23]([OH:24])[C:25]4[CH:30]=[CH:29][C:28]([C:43]5[CH:42]=[CH:41][CH:40]=[C:39]([S:36]([CH3:35])(=[O:38])=[O:37])[CH:44]=5)=[CH:27][N:26]=4)[CH2:17][CH2:16]3)=[CH:8][C:9]=2[C:11]([F:14])([F:13])[F:12])[S:4][C:3]=1[C:32]([NH2:34])=[O:33]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 21064678HCID 21064678, compound

Product 1

HCID 21064694HCID 21064694, compoundYield 42.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A N2-purged suspension of 3-Amino-6-{4-[2-(5-bromo-pyridin-2-yl)-2-hydroxy-ethylamino]-piperidin-1-yl}-4-trifluoromethyl-thieno[2,3-b]pyridine-2-carboxylic acid amide (60 mg, 0.107 mmol), (3-methylsulfonylphenyl)boronic acid (24 mg, 0.118 mmol), tetrakis(triphenylphosphine)palladium(0) (19 mg, 0.016 mmol), and potassium carbonate (30 mg, 0.214 mmol) in dry DMF (4 ml) and water (1 ml) was sealed and heated to 85° C. for 18h. The crude reaction mixture was applied to a celite plug and purified by SiO2 chromatography (0–25% MeOH/CH2Cl2 with 1% NH4OH). Fractions containing product were pooled and concentrated. The solid yellow residue was dissolved in 1 ml DMF, applied to a 2 mm prep plate (Merck) and eluted twice with 10% MeOH/CH2Cl2 with 1% NH4OH. The recovered yellow residue was dissolved in 0.5 ml water, 2 ml MeOH, 10 ml CH2Cl2, and 10 ml EtOAc and crystallized by the addition of 50 ml hexanes to give 29.0 mg, 42.3% of 3-Amino-6-(4-{2-hydroxy-2-[5-(3-methanesulfonyl-phenyl)-pyridin-2-yl]-ethylamino}-piperidin-1-yl)-4-trifluoromethyl-thieno[2,3-b]pyridine-2-carboxylic acid amide product. ES+ 635.1 m/z (MH+).

Workup

  1. customA N2-purged
  2. customwas sealed
  3. customThe crude reaction mixture
  4. custompurified by SiO2 chromatography (0–25% MeOH/CH2Cl2 with 1% NH4OH)
  5. additionFractions containing product
  6. concentrationconcentrated
  7. dissolutionThe solid yellow residue was dissolved in 1 ml DMF
  8. washeluted twice with 10% MeOH/CH2Cl2 with 1% NH4OH
  9. dissolutionThe recovered yellow residue was dissolved in 0.5 ml water
  10. custom2 ml MeOH, 10 ml CH2Cl2, and 10 ml EtOAc and crystallized by the addition of 50 ml hexanes

Sources & evidence

ORD record
ord-e63d05d588d84e58958e9635621d764f
Source dataset
uspto-grants-2006_10
Patent number
US07119102B2

Reaction notes

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