Tetrahydrofuran → HCID 178505152, compound

HRID 2089065Notes

Reaction equation

HRID 2089065 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.[CH3:34][S:35](Cl)(=[O:37])=[O:36].CCN(C(C)C)C(C)C.[CH2:48]1[CH2:52][O:51]CC1>O>[C:52]([O-:18])(=[O:51])[CH3:48].[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][S:35]([CH3:34])(=[O:37])=[O:36])[CH2:31][CH2:32]2)[N:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178511663HCID 178511663, compound

Product 2

HCID 517165Ammonium AcetateHCID 178505152HCID 178505152, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of Example 275a (350 mg, crude, ˜0.414 mmol), methanesulfonyl chloride (95 mg, 0.828 mmol), and Hunig's base (0.217 mL, 1.242 mmol) in THF (4 mL) was stirred at room temperature for 1 day then concentrated in vacuo. To the residue was added dioxane (5 mL) and NaOH (20%, 1 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 provide the title compound (15 mg, 0.036 mmol, 9% yield). MS (ESI) m/e 421 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 1.35-1.51 (m, 4H) 1.98-2.09 (m, 4H) 2.91 (s, 3H) 3.14-3.23 (m, J=8.24 Hz, 1H) 3.71-3.83 (m, J=10.07 Hz, 1H) 6.66-6.76 (m, 1H) 7.04 (d, J=7.63 Hz, 1H) 7.08 (s, 1H) 7.18 (dd, J=7.93, 4.88 Hz, 1H) 8.29 (dd, J=4.58, 1.83 Hz, 1H) 8.34 (s, 1H) 8.78 (d, J=7.94 Hz, 1H).

Workup

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

Sources & evidence

ORD record
ord-2eff0f365b2646f19cbe36d05aca2201
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Reaction notes

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