Methyl iodide → HCID 23506070, compound

HRID 1840176Notes

Reaction equation

HRID 1840176 reaction equation
COC1C=CC([NH:9][C:10]2[CH:11]=[C:12]([N:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]([F:37])([F:36])[CH:33]([F:35])[F:34])[CH:26]=3)[CH2:17][CH:18]([OH:23])[C:19]([F:22])([F:21])[F:20])[CH:13]=[CH:14][CH:15]=2)=CC=1.CI.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:46][O:47][C:48]1[CH:53]=[CH:52][C:51]([CH2:54]NC2C=C(CC(NCC3C=CC=C(OC(F)(F)C(F)F)C=3)(O)C(F)(F)F)C=CC=2)=[CH:50][CH:49]=1>O1CCCC1>[CH3:46][O:47][C:48]1[CH:53]=[CH:52][C:51]([CH2:54][NH:9][C:10]2[CH:11]=[C:12]([N:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]([F:37])([F:36])[CH:33]([F:34])[F:35])[CH:26]=3)[CH2:17][CH:18]([OH:23])[C:19]([F:22])([F:20])[F:21])[CH:13]=[CH:14][CH:15]=2)=[CH:50][CH:49]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 235060283-[[3-[(4-Methoxyphenyl)amino]phenyl]-[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanolHCID 131724296HCID 131724296, compound

Product 1

HCID 23506070HCID 23506070, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 3-[[3-[(4methoxyphenyl)amino]phenyl]-[[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol (44.3 mg, 0.083 mmol) in tetrahydrofuran (1.0 mL), methyl iodide (6.21 μL, 0.099 mmol) and cesium carbonate (36.6 mg, 0.112 mmol) were added. The dark solution was stirred at 23° C. for 2 h, then heated to 55° C. for 12 h. The reaction mixture was filtered through celite, and the residue was purified by silica gel chromatography eluting with 20% ethyl acetate in hexane to give 25.2 mg (55%) of the desired 3-[[3-[(4methoxyphenyl)methylamino]-phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methylamino]-1,1,1-trifluoro-2-propanol product as an orange oil. HRMS calcd for C26H25F7N2O3: 546.1753, found: 546.1750 [M]+. 1H NMR (CDCl3), δ 3.54 (m, 1H), 3.38 (s, 3H), 3.65-3.80 (m, 4H), 4.59 (s, 2H), 5.90 (tt, 1H), 6.20 (d, 1H), 6.37 (d, 1H), 6.68 (s, 1H), 6.76 (d, 2H), 6.90-7.15 (m, 6H), 7.31 (t, 1H). 19F NMR (CDCl3), δ −137.21 (d, 2F), −88.52 (s, 2F), −78.79 (s, 3F).

Workup

  1. temperatureheated to 55° C. for 12 h
  2. filtrationThe reaction mixture was filtered through celite
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with 20% ethyl acetate in hexane
  5. customto give 25.2 mg (55%) of the

Sources & evidence

ORD record
ord-f5de2de7f3444dedbb3ac373b751f1d6
Source dataset
uspto-grants-2004_01
Patent number
US06677379B2

Reaction notes

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