Water → HCID 86670718, compound

HRID 878057Notes

Reaction equation

HRID 878057 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][CH3:9])=[C:4]([I:10])[CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:21][C:22]([F:37])([F:36])[C:23]1[CH:24]=[C:25]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[C:26](Cl)=[O:27].O>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:9])[C:26](=[O:27])[C:25]2[CH:24]=[C:23]([C:22]([F:37])([F:36])[F:21])[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=2)=[C:4]([I:10])[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 574434006-chloro-4-iodo-N-methylpyridin-3-amine

Product 1

HCID 86670718HCID 86670718, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (6-chloro-4-iodo-pyridin-3-yl)-methyl-amine (300 mg, 1.12 mmol, prepared according to WO2006013050) in THF (3 mL) was added dropwise at −78° C. lithium bis(trimethylsilyl)amide (1M solution in THF, 1.17 mL, 1.17 mmol). The reaction mixture was stirred at −78° C. for 30 minutes. Then, 3,5-bis(trifluoromethyl)benzoyl chloride (340 mg, 1.23 mmol, CAS RN 1271-19-8) was added at −78° C. and the reaction was stirred for 30 minutes at this temperature. The reaction mixture was allowed to warm to room temperature, stirred for another 1 hour and then poured on 30 mL H2O and 30 mL EtOAc. The layers were separated and the aqueous layer was extracted a second time with 30 mL EtOAc. The combined organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 70:30). Colorless solid (328 mg, 57.7%). MS (TurboSpray): m/z=508.0 [M+H]+.

Workup

  1. stirringthe reaction was stirred for 30 minutes at this temperature
  2. temperatureto warm to room temperature
  3. stirringstirred for another 1 hour
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted a second time with 30 mL EtOAc
  6. washThe combined organic layers were washed with 30 mL brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with a gradient of n-heptane:EtOAc (100:0 to 70:30)

Sources & evidence

ORD record
ord-c80f5d7a66c946ecba09848c76ca10a0
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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