Water → HCID 68737970, compound

HRID 240790Notes

Reaction equation

HRID 240790 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:12]=[N:13][N:14]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH:15]=3)[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.[N:30]([CH2:33][CH2:34][CH3:35])=[C:31]=[O:32].[N-]=C=O.O>N1C=CC=CC=1>[CH2:16]([N:14]1[CH:15]=[C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[NH:1][C:31]([NH:30][CH2:33][CH2:34][CH3:35])=[O:32])[N:12]=[N:13]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 61033Propyl isocyanateHCID 105034IsocyanateHCID 68737159HCID 68737159, compound

Product 1

HCID 68737970HCID 68737970, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of Example 64A (75 mg, 0.19 mmol) in pyridine (2 mL) was added 1-isocyanatopropane (16 mg, 0.19 mmol) and the reaction mixture was stirred at ambient temperature for about 3 hours. Additional isocyanate (0.1 mL) was added and the mixture was heated at about 80° C. for about 16 hours. The reaction mixture was cooled to ambient temperature and water (5 mL) was added. The resulting precipitate was collected by filtration then treated with hydrochloric acid (4 N solution in dioxane, 3 mL) and stirred at room temperature for about 4.5 hours. Diethyl ether (5 mL) was added and the precipitate collected by filtration. The crude material was purified by reverse-phase HPLC using acetonitrile/water (0.05 M ammonium acetate) gradient elution method to afford the title compound as the acetate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.34 (s, 1H), 8.50 (s, 1H), 8.42 (s, 1H), 7.80 (d, J=8.7 Hz, 1H), 7.38 (d, J=8.7 Hz, 1H), 7.31-7.48 (m, 5H), 5.65 (s, 2H), 3.18 (dd, J=6.6, 12.7 Hz, 2H), 1.51 (dd, J=7.1, 14.3 Hz, 2H), 0.91 (t, J=7.3 Hz, 3H). MS (ESI+) m/z 376 (M+H)+.

Workup

  1. temperaturethe mixture was heated at about 80° C. for about 16 hours
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationThe resulting precipitate was collected by filtration
  4. additionthen treated with hydrochloric acid (4 N solution in dioxane, 3 mL)
  5. stirringstirred at room temperature for about 4.5 hours
  6. additionDiethyl ether (5 mL) was added
  7. filtrationthe precipitate collected by filtration
  8. customThe crude material was purified by reverse-phase
  9. washacetonitrile/water (0.05 M ammonium acetate) gradient elution method

Sources & evidence

ORD record
ord-f0618081cb6f4aa2a6276c27114d3c00
Source dataset
uspto-grants-2014_02
Patent number
US08648069B2

Reaction notes

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