Tetrahydrofuran → HCID 178485943, compound

HRID 2089066Notes

Reaction equation

HRID 2089066 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10](S(C3C=CC=CC=3)(=O)=[O:18])[CH:9]=2)[N:5]=[C:4]([NH:26][C@H:27]2[CH2:32][CH2:31][C@H:30]([NH2:33])[CH2:29][CH2:28]2)[N:3]=1.[N:34]([CH3:37])=[C:35]=[O:36].CCN(C(C)C)C(C)C.[CH2:47]1[CH2:51][O:50]CC1>O>[C:51]([O-:18])(=[O:50])[CH3:47].[NH4+:3].[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[N:5]=[C:4]([NH:26][C@H:27]2[CH2:28][CH2:29][C@H:30]([NH:33][C:35]([NH:34][CH3:37])=[O:36])[CH2:31][CH2:32]2)[N:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 12228Methyl IsocyanateHCID 81531DiisopropylethylamineHCID 178511663HCID 178511663, compound

Product 2

HCID 517165Ammonium AcetateHCID 178485943HCID 178485943, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of Example 275a (150 mg, 0.311 mmol), isocyanatomethane (21.26 mg, 0.373 mmol) and Hunig's base (0.108 mL, 0.621 mmol) in THF (4 mL) was stirred at room temperature for 16 hours. The resulting mixture was concentrated in vacuo. To the residue was added dioxane (5 mL) and NaOH (20%, 0.6 mL) and heated at 80° C. for 1 hour. The reaction mixture was concentrated and purified by reverse-phase HPLC performed on a Phenomenex Luna C8 AXIA column (30×75 mm, 100 Å) using a gradient of 10% to 95% acetonitrile: 10 mM ammonium acetate in water over 12 minutes at a flow rate of 50 mL/minutes to provide the title compound (10 mg, 0.025 mmol, 8% yield). MS (ESI) m/e 400 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 1.21-1.49 (m, 4H) 1.89-1.96 (m, 2H) 1.99-2.08 (m, J=10.68 Hz, 2H) 2.57 (d, J=4.58 Hz, 3H) 3.34-3.45 (m, 1H) 3.74-3.84 (m, 1H) 5.41-5.47 (m, J=4.27 Hz, 1H) 5.52 (d, J=7.63 Hz, 1H) 7.02 (d, J=7.63 Hz, 1H) 7.07 (s, 1H) 7.17 (dd, J=7.93, 4.58 Hz, 1H) 8.29 (dd, J=4.58, 1.53 Hz, 1H) 8.34 (s, 1H) 8.79 (d, J=7.32 Hz, 1H).

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. additionTo the residue was added dioxane (5 mL) and NaOH (20%, 0.6 mL)
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-058a0c9522494a02a21b3bf8d68c1523
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Reaction notes

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