Sodium Carbonate → HCID 45274382, compound

HRID 1622394Notes

Reaction equation

HRID 1622394 reaction equation
Cl[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:17])[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>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.C(#N)C>[Cl:17][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:19]2[S:18][CH:22]=[CH:21][CH:20]=2)[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 28116401-(3,5-Dichloropyridin-4-yl)piperidine-4-carboxamide

Product 1

HCID 45274382HCID 45274382, compoundYield 10.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

General procedure E was followed using 1-(3,5-dichloropyridin-4-yl)piperidine-4-carboxamide 23 (75 mg, 0.27 mmol), 2-thiophene boronic acid (44 mg, 0.34 mmol), tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.014 mmol), acetonitrile (3 mL) and 0.5 M sodium carbonate (0.77 mL, 0.38 mmol). The crude product was purified by flash column chromatography on silica gel (CH2Cl2, EtOH, 96:4-80:20, biotage 25+S) to yield the a mixture of starting material and product (50 mg, 2:5), along with dehalogenated monochloro starting material (7 mg, 11%). The product/starting material mixture was further purified by preparative hplc (CH3CN, H2O, gradient 1:9 to 9:1, 15 min) to furnish the title compound (9 mg, 10%) as a clear colourless oil, along with recovered 1-(3,5-dichloropyridin-4-yl)piperidine-4-carboxamide (30 mg, 40%) as a white solid, LC-MS (ESI, 4 min) Rt 2.31 min, m/z 322 (100%, [M+H]+); m/z (ESI) C15H16N3OSCl requires 321.0703, found [M+H]+ 321.0700.

Workup

  1. customThe crude product was purified by flash column chromatography on silica gel (CH2Cl2, EtOH, 96:4-80:20, biotage 25+S)
  2. customto yield
  3. additionthe a mixture of starting material and product (50 mg, 2:5)
  4. customThe product/starting material mixture was further purified by preparative hplc (CH3CN, H2O, gradient 1:9 to 9:1, 15 min)

Sources & evidence

ORD record
ord-0b209e4220f744b28f5af051c58d98d1
Source dataset
uspto-grants-2014_07
Patent number
US08778925B2

Reaction notes

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