Cyclopropanecarbonyl chloride → HCID 50940100, compound

HRID 2089062Notes

Reaction equation

HRID 2089062 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][CH:27]2[CH2:32][CH2:31][CH2:30][CH:29]([NH2:33])[CH2:28]2)[N:3]=1.[CH:34]1([C:37](Cl)=[O:38])[CH2:36][CH2:35]1.CCN(C(C)C)C(C)C>C1COCC1.O>[C:37]([O-:38])(=[O:18])[CH3:34].[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][CH:27]2[CH2:32][CH2:31][CH2:30][CH:29]([NH:33][C:37]([CH:34]3[CH2:36][CH2:35]3)=[O:38])[CH2:28]2)[N:3]=1

Participants

7

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 87192197HCID 87192197, compound

Product 2

HCID 517165Ammonium AcetateHCID 50940100HCID 50940100, compoundYield 15.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of Example 270a (350 mg, crude, ˜0.414 mmol) and cyclopropanecarbonyl chloride (43.3 mg, 0.414 mmol), Hunig's base (0.217 mL, 1.242 mmol) in THF (4 ml) was stirred at room temperature for 2 hours and then concentrated in vacuo. To the residue was added dioxane (5 mL) and NaOH (20%, 0.8 mL) and heated at 90° C. for 3 hours. 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 give the title compound (13 mg, 7.6% yield). MS (ESI) m/e 411 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 0.54-0.63 (m, 2H) 0.63-0.72 (m, 2H) 1.09-1.58 (m, 5H) 1.73-1.88 (m, 2H) 1.97 (s, 1H) 2.18 (s, 1H) 3.68-3.78 (m, 1H) 3.79-3.92 (m, J=7.93 Hz, 1H) 7.04-7.13 (m, 2H) 7.19 (dd, J=7.93, 4.58 Hz, 1H) 7.57-7.69 (m, 1H) 8.27 (dd, J=4.73, 1.37 Hz, 1H) 8.34 (s, 1H) 8.75 (d, J=7.93 Hz, 1H) 12.00 (s, 1H).

Workup

  1. concentrationconcentrated in vacuo
  2. additionTo the residue was added dioxane (5 mL) and NaOH (20%, 0.8 mL)
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-fe86931e63474d7b999492a6ff2e2a2d
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Reaction notes

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