Methyl iodide → 5-(3-{1-[1-(diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorophenyl)-1-methyl-1H-tetrazole

HRID 603003Notes

Reaction equation

HRID 603003 reaction equation
[C:1]1([CH:7]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:8]2[CH2:11][CH:10]([CH:12]([C:17]3[CH:18]=[C:19]([C:24]4[NH:28][N:27]=[N:26][N:25]=4)[CH:20]=[C:21]([F:23])[CH:22]=3)[C:13]([F:16])([CH3:15])[CH3:14])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CI.[CH3:37]CN(C(C)C)C(C)C>CC#N>[C:29]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]2[CH2:11][CH:10]([CH:12]([C:17]3[CH:18]=[C:19]([C:24]4[N:28]([CH3:37])[N:27]=[N:26][N:25]=4)[CH:20]=[C:21]([F:23])[CH:22]=3)[C:13]([F:16])([CH3:15])[CH3:14])[CH2:9]2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 81531DiisopropylethylamineHCID 178455675HCID 178455675, compound

Product 1

HCID 167449255-(3-{1-[1-(diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorophenyl)-1-methyl-1H-tetrazole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The reaction of mixture of 1.31 g (2.85 mmol) 5-(3-{1-[1-(diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorophenyl)-1H-tetrazole, 0.36 mL (5.70 mmol) methyl iodide, and 1.77 mL (9.97 mmol) DIEA in 8 mL MeCN was heated to reflux for 2.5 h. Then it was concentrated to remove the solvents. Then it was added 20 mL of CH2Cl2 and 5 mL of water and adjust pH=7-8 with aq NaHCO3. The water layer was extracted with CH2Cl2, and the combined organic layer was concentrated. The residue was separated by silica gel chromatography with CH2Cl2/MeOH/NH3 (2M) in MeOH to afford the title compound; 1H-NMR(CDCl3) δ 1.22(d, 3H, J=22 Hz), 1.29(d, 3H, J=22 Hz), 2.37 (t, 1H, J=8 Hz), 2.90 (t, 1H, J=8 Hz), 3.00 (m, 1H), 3.14 (m, 1H), 3.22 (m, 1H), 3.68 (J, 1H, J=6 Hz), 4.19 (s, 3H), 4.26 (s, 1H), 7.12-7.43 (m, 13H); Mass Spectrum: m/e=474 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2.5 h
  3. concentrationThen it was concentrated
  4. customto remove the solvents
  5. additionThen it was added 20 mL of CH2Cl2 and 5 mL of water
  6. extractionThe water layer was extracted with CH2Cl2
  7. concentrationthe combined organic layer was concentrated
  8. customThe residue was separated by silica gel chromatography with CH2Cl2/MeOH/NH3 (2M) in MeOH

Sources & evidence

ORD record
ord-e26d76d6fcd24df295b9db9531bda5a5
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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