Triethylamine → 1-((1R,2S)-2-(((3-(4-fluorophenyl)propyl)(methyl)amino)methyl)cyclohexyl)-3-(3-(1-methyl-1H-tetrazol-5-yl)phenyl)urea

HRID 1592328Notes

Reaction equation

HRID 1592328 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]([CH2:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]2[NH2:20])[CH3:12])=[CH:4][CH:3]=1.C(N(CC)CC)C.C1([O:34][C:35](=O)[NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([C:43]3[N:47]([CH3:48])[N:46]=[N:45][N:44]=3)[CH:38]=2)C=CC=CC=1>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][N:11]([CH2:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]2[NH:20][C:35]([NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([C:43]3[N:47]([CH3:48])[N:46]=[N:45][N:44]=3)[CH:38]=2)=[O:34])[CH3:12])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22252681phenyl 3-(1-methyl-1H-tetraazol-5-yl)phenylcarbamateHCID 69426356(1R,2S)-2-({[3-(4-fluorophenyl)-propyl]-methyl-amino}-methyl)-cyclohexylamine

Product 1

HCID 112369501-((1R,2S)-2-(((3-(4-fluorophenyl)propyl)(methyl)amino)methyl)cyclohexyl)-3-(3-(1-methyl-1H-tetrazol-5-yl)phenyl)ureaYield 60.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (1R,2S)-2-({[3-(4-fluorophenyl)-propyl]-methyl-amino}-methyl)-cyclohexylamine (72 mg, 259 μmol) in acetonitrile (2 mL) was treated with triethylamine (72 μL, 517 μmol) and [3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester (76 mg, 259 μmol). The mixture was stirred at room temperature for 15.5 hours and then was concentrated under vacuum. The residue was dissolved in ethyl acetate, and the solution was washed sequentially with 1.0 M aqueous sodium hydroxide, water and saturated aqueous sodium chloride. The organic phase was dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography, eluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide, to provide a white amorphous solid (75 mg, 60%).

Workup

  1. concentrationwas concentrated under vacuum
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washthe solution was washed sequentially with 1.0 M aqueous sodium hydroxide, water and saturated aqueous sodium chloride
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash chromatography
  7. washeluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide

Sources & evidence

ORD record
ord-690b5b8d2d114d08b29bf7cd0069351d
Source dataset
uspto-grants-2007_11
Patent number
US07291744B2

Reaction notes

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