Triethylamine → HCID 70663289, compound

HRID 878296Notes

Reaction equation

HRID 878296 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:31])[C:15](=[O:30])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([S:26][CH2:27][CH2:28]O)[CH:17]=2)=[C:4]([O:32][CH3:33])[CH:3]=1.C([N:36]([CH2:39][CH3:40])[CH2:37]C)C.CS(Cl)(=O)=O.C([O-])(O)=O.[Na+].N1CCC1.[NH4+].[Cl-]>C(Cl)Cl.CCOC(C)=O>[N:36]1([CH2:28][CH2:27][S:26][C:18]2[CH:17]=[C:16]([CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=2)[C:15]([N:14]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=2[O:32][CH3:33])[CH3:31])=[O:30])[CH2:37][CH2:40][CH2:39]1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 10422AzetidineHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 70663250HCID 70663250, compound

Product 1

HCID 70663289HCID 70663289, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cold solution of N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-3-(2-hydroxyethylthio)-N-methyl-5-(trifluoromethyl)benzamide (0.16 g, 333 μmol, example 216) in CH2Cl2 (2 mL) were added triethylamine (50.5 mg, 69.6 μL, 500 μmol) and methanesulfonyl chloride (38.1 mg, 25.8 μL, 333 μmol) and the clear colorless solution was stirred at 0° C. for 3.75 hours. The reaction mixture was poured on saturated aqueous NaHCO3 solution and CH2Cl2 and the layers were separated. The aqueous layer was extracted twice with CH2Cl2. The organic layers were washed once with brine, dried over MgSO4, filtered, and evaporated. The intermediate mesylate was dissolved in isopropylacetate (2.0 mL), treated with azetidine (41.8 mg, 49.4 μL, 733 μmol) and heated to reflux (oil bath 95° C.) for 16 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered and evaporated. The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless solid (0.055 g; 31%). MS (ESI): m/z=520.17 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with CH2Cl2
  3. washThe organic layers were washed once with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe intermediate mesylate was dissolved in isopropylacetate (2.0 mL)
  8. temperatureheated
  9. temperatureto reflux (oil bath 95° C.) for 16 hours
  10. customthe layers were separated
  11. extractionThe aqueous layer was extracted twice with EtOAc
  12. dry with materialThe organic layers were dried over MgSO4
  13. filtrationfiltered
  14. customevaporated
  15. customThe product was purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-4ea5189e1fec4823a1ca89e8a2266f48
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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