Triethylamine → HCID 25190071, compound

HRID 1692434Notes

Reaction equation

HRID 1692434 reaction equation
[CH3:1][C:2]1[C:3]([C:24]([OH:26])=O)=[C:4]([C:18]2[CH:19]=[N:20][CH:21]=[N:22][CH:23]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[CH:7]=1.C(Cl)(=O)C(Cl)=O.CCN(CC)CC.[N:40]1([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:44][CH2:43][CH2:42][CH2:41]1>CN(C=O)C>[CH3:1][C:2]1[C:3]([C:24]([N:48]2[CH2:49][CH2:50][CH:45]([N:40]3[CH2:44][CH2:43][CH2:42][CH2:41]3)[CH2:46][CH2:47]2)=[O:26])=[C:4]([C:18]2[CH:19]=[N:20][CH:21]=[N:22][CH:23]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:16])[F:17])[CH:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 787034-(1-Pyrrolidinyl)piperidineHCID 66901646HCID 66901646, compound2×

Product 1

HCID 25190071HCID 25190071, compoundYield 99.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Conditions

Temperature
0 °C

Procedure

0.05 g (0.1 mmol) of 5-methyl-3-pyrimidin-5-yl-3′-trifluoromethyl-biphenyl-4-carboxylic acid (intermediate 11) in 1.0 ml of oxalyl chloride (11.7 mmol) was treated at RT while stirring with one drop of DMF; after 30 min, the excess of oxalyl chloride was removed by evaporation in a high vacuum at RT. The residue was dissolved in 2.0 ml of CH2Cl2 and cooled down to 0° C.; then, 0.08 ml=0.056 g (0.6 mmol) of Et3N was added while stirring, followed by 0.022 g (0.1 mmol) of 4-pyrrolidin-1-yl-piperidine. The reaction mixture was subsequently warmed up to RT. After two hours, it was poured into crashed ice and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1) to give 0.049 g (71%) of the title compound as yellow solid. MS: 495.3 (MH+).

Workup

  1. customthe excess of oxalyl chloride was removed by evaporation in a high vacuum at RT
  2. dissolutionThe residue was dissolved in 2.0 ml of CH2Cl2
  3. temperatureThe reaction mixture was subsequently warmed up to RT
  4. waitAfter two hours
  5. additionit was poured
  6. extractionextracted twice with CH2Cl2
  7. washthe organic phases were washed with water
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 4:1)

Sources & evidence

ORD record
ord-4a885989c793462c8c2b8ee5ad2da841
Source dataset
uspto-grants-2012_04
Patent number
US08153805B2

Reaction notes

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