Methanol → N-(3-acetylphenyl)-N'-{(4aSR,8SR,8aRS)-2-[3-(4-fluorophenyl)propyl]-decahydroisoquinolin-8-yl}urea

HRID 1766399Notes

Reaction equation

HRID 1766399 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:20][CH2:19][CH:18]3[CH:13]([CH:14]([NH2:21])[CH2:15][CH2:16][CH2:17]3)[CH2:12]2)=[CH:4][CH:3]=1.[C:22]([C:25]1[CH:26]=[C:27]([N:31]=[C:32]=[O:33])[CH:28]=[CH:29][CH:30]=1)(=[O:24])[CH3:23].CO>O1CCCC1>[C:22]([C:25]1[CH:26]=[C:27]([NH:31][C:32]([NH:21][CH:14]2[CH:13]3[CH:18]([CH2:19][CH2:20][N:11]([CH2:10][CH2:9][CH2:8][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[CH2:12]3)[CH2:17][CH2:16][CH2:15]2)=[O:33])[CH:28]=[CH:29][CH:30]=1)(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 887MethanolHCID 3127181-(3-Isocyanatophenyl)ethan-1-oneHCID 69412580(4aSR,8SR,8aRS)-2-[3-(4-fluorophenyl)propyl]decahydroisoquinolin-8-amine

Product 1

HCID 69414162N-(3-acetylphenyl)-N'-{(4aSR,8SR,8aRS)-2-[3-(4-fluorophenyl)propyl]-decahydroisoquinolin-8-yl}ureaYield 50.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (4aSR,8SR,8aRS)-2-[3-(4-fluorophenyl)propyl]decahydroisoquinolin-8-amine (15 mg, 50 μmol) in tetrahydrofuran (1 mL) was treated with 3-acetylphenylisocyanate (8.3 mg, 50 mmol). The mixture was stirred for 30 minutes, then treated with methanol (0.5 mL). The mixture was concentrated under vacuum to provide a residue. The residue was purified by flash column chromatography, eluting with 5% triethylamine/ethyl acetate, to provide a white solid (11.4 mg, 49%). 1H NMR (300 MHz, CDCl3) δ7.80 (s, 1H), 7.78 (d, J=8 Hz, 1H), 7.70 (s, 1H), 7.50 (d, J=8 Hz, 1H), 7.29 (t, J=8 Hz, 1H), 7.00 (m, 2H), 6.83 (m, 2H), 5.16 (d, J=10 Hz, 1H), 3.61 (m, 1H), 3.42 (m, 1H), 3.08 (m, 1H), 2.94 (m, 1H), 2.53 (s, 3H), 2.47 (t, J=8 Hz, 2H), 2.4-2.2 (m, 2H), 1.9-1.5 (m, 8H), 1.4-0.8 (m, 5H). Mass spec (ES+) m/z 452.3 (M+H+, 100%).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. customto provide a residue
  3. customThe residue was purified by flash column chromatography
  4. washeluting with 5% triethylamine/ethyl acetate

Sources & evidence

ORD record
ord-eecc0d2c7c6844b5860c64ae463d09be
Source dataset
uspto-grants-2007_06
Patent number
US07230022B2

Reaction notes

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