Hexylamine → HCID 59352478, compound

HRID 2385524Notes

Reaction equation

HRID 2385524 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:24]3[C:15](=[CH:16][C:17]4[O:22][CH2:21][CH2:20][O:19][C:18]=4[CH:23]=3)[O:14][CH2:13]1)[C:5](=[O:12])[N:6]2[CH3:11].ClC([O:28][C:29](Cl)(Cl)Cl)=O.[CH2:33]([NH2:39])[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38].C(N(CC)CC)C>O1CCOCC1>[CH2:33]([NH:39][C:29]([NH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:24]3[C:15](=[CH:16][C:17]4[O:22][CH2:21][CH2:20][O:19][C:18]=4[CH:23]=3)[O:14][CH2:13]1)[C:5](=[O:12])[N:6]2[CH3:11])=[O:28])[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]

Participants

6

Reactant 4

HCID 8102HexylamineHCID 8471TriethylamineHCID 10426DiphosgeneHCID 59352092HCID 59352092, compound

Product 1

HCID 59352478HCID 59352478, compoundYield 65.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 4′-amino-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.33 g, 1.00 mmol) in 1,4-dioxane (20 mL) was added trichloromethyl chloroformate (0.14 mL, 1.2 mmol). The reaction mixture was heated at 65° C. for 24 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (10 mL) and the resultant solution was cooled to 0° C. in an ice bath. n-Hexylamine (0.40 mL, 3.0 mmol) and triethylamine (0.70 mL, 5.0 mmol) were added. The reaction mixture was allowed to warm to ambient temperature, stirred for 24 h and concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water (4×150 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was recrystallized from ethyl acetate/hexanes to afford 1-hexyl-3-(1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-4′-yl)urea (0.294 g, 64%) as a pale brown solid: mp 154-155° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 7.78-7.75 (m, 1H), 7.30-7.25 (m, 1H), 6.63-6.60 (m, 1H), 6.52 (s, 1H), 6.34 (s, 1H), 6.09 (s, 1H), 4.76 (ABq, 2H), 4.22-4.11 (m, 5H), 3.28 (s, 3H), 3.14-3.00 (m, 2H), 1.48-1.41 (m, 2H), 1.32-1.25 (m, 6H), 0.89 (t, J=6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 176.3, 154.6, 154.2, 145.1, 142.8, 139.4, 135.9, 129.8, 119.0, 118.3, 115.8, 112.2, 103.3, 99.3, 78.2, 64.5, 63.8, 57.1, 40.5, 31.5, 29.8, 27.0, 26.4, 22.5, 14.0; MS (ES+) m/z 452.2 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
  4. temperaturethe resultant solution was cooled to 0° C. in an ice bath
  5. temperatureto warm to ambient temperature
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. washwashed with water (4×150 mL)
  9. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-8994cd5f803a4ebeb7919aaf6c62e0fe
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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