Hexyl isocyanate → HCID 178444879, compound

HRID 1795063Notes

Reaction equation

HRID 1795063 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]1[CH2:18][CH2:17][C@H:16]([NH2:19])[CH2:15][CH2:14]1)[C:10]([O-:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:20]([N:26]=[C:27]=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].[CH:29](N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]1[CH2:18][CH2:17][C@H:16]([NH:19][C:27]([NH:26][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[O:28])[CH2:15][CH2:14]1)[C:10]([O:12][CH3:29])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 75659Hexyl isocyanateHCID 81531DiisopropylethylamineHCID 178454234HCID 178454234, compound

Product 1

HCID 178444879HCID 178444879, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

317 mg (1 mmol) of trans-(2S)-[(tert-butoxycarbonyl)amino](4-azidocyclohexyl)ethanoate was reduced using an identical procedure to that described in Example 1, Step C to yield 290 mg of trans-(2S)-[(tert-butoxycarbonyl)amino](4-aminocyclohexyl)ethanoate. To a solution of 30 mg (0.1 mmol) of trans-(2S)-[(tert-butoxycarbonyl)amino](4-aminocyclohexyl)ethanoate in 1 mL of methylene chloride at 0° C. was added 0.018 mL (0.125 mmol) of hexyl isocyanate and 0.044 mL (0.25 mmol) of diisopropylethylamine (DIEA). The mixture was stirred at ambient temperature for 16 h, concentrated in vacuo, and diluted with ethyl acetate. The organic phase was washed with saturated aqueous sodium bicarbonate solution, brine, dried over magnesium sulfate and the solvent removed in vacuo to yield methyl trans-(2S)-[(tert-butoxycarbonyl)amino](4-{[(hexylamino)carbonyl]amino}cyclohexyl)-ethanoate which was used without further purification. To this material, dissolved in 1 mL of THF, was added 21 mg (0.5 mmol) of lithium hydroxide in 1 mL of water and the reaction was stirred for 16 h and concentrated in vacuo. The aqueous solution was acidified with 2N hydrochloric acid and extracted three times with ethyl acetate. The combined organic phase was washed with brine, dried over magnesium sulfate, and concentrated in vacuo to give the carboxylic acid which was dissolved in 1 mL of dimethylformamide (DMF). To this was added 0.008 mL (0.1 mmol) of thiazolidine, 23 mg (0.12 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), 21 mg (0.15 mmol) of 1-hydroxybenzotriazole hydrate (HOBT), and 0.042 mL (0.25 mmol) of diisopropylethylamine (DIEA). The mixture was stirred for 16 h and diluted with ethyl acetate. The organic phase was washed with water, saturated aqueous sodium bicarbonate solution, water, brine, dried over magnesium sulfate and the solvent removed in vacuo to yield 53 mg The product was deprotected as described in Example 1, Step D, to give 22 mg of the title compound. 1H NMR (400 MHz, CD3OD) δ 4.70–4.66 (m, 0.45H), 4.61–4.57 (m, 1H), 4.5–4.46 (m, 0.55H), 3.93–3.86 (m, 0.55H), 3.83–3.71 (m, 1.45H), 3.46 (d, 0.45H, J=7 Hz), 3.42–3.35 (m, 1.55H), 3.16–3.02 (m, 4H), 1.98–1.90 (m, 3H), 1.64–1.58 (m, 1H), 1.56–1.39 (m, 3H), 1.39–1.23 (m, 7H), 1.23–1.06 (m, 3H), 0.95–0.87 (m, 3H).

Workup

  1. concentrationconcentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washThe organic phase was washed with saturated aqueous sodium bicarbonate solution, brine
  4. dry with materialdried over magnesium sulfate
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-99787f198ff84be885e29287b77aacac
Source dataset
uspto-grants-2006_04
Patent number
US07026316B2

Reaction notes

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