Trifluoroacetic acid → HCID 178527587, compound

HRID 2089067Notes

Reaction equation

HRID 2089067 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)[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.[CH:34]1([S:37](Cl)(=[O:39])=[O:38])[CH2:36][CH2:35]1.C(N(CC)CC)C.[F:48][C:49]([F:54])([F:53])[C:50]([OH:52])=[O:51]>C1COCC1>[F:48][C:49]([F:54])([F:53])[C:50]([OH:52])=[O:51].[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[CH2:32][CH2:31][C@H:30]([NH:33][S:37]([CH:34]3[CH2:36][CH2:35]3)(=[O:39])=[O:38])[CH2:29][CH2:28]2)[N:3]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 2760919Cyclopropanesulfonyl chlorideHCID 178511663HCID 178511663, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 178527587HCID 178527587, compoundYield 9.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of Example 275a (350 mg, crude, 0.414 mmol), cyclopropanesulfonyl chloride (116 mg, 0.828 mmol), and triethylamine (0.058 mL, 0.414 mmol) in THF (5 mL) was stirred at room temperature for 1 day and concentrated in vacuo. To the residue was added dioxane (5 mL) and NaOH (20%, 1 mL) and the mixture was heated at 85° 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: 0.1% aqueous trifluoroacetic acid over 12 minutes at a flow rate of 50 mL/minutes to give the title compound (17 mg, 9.2% yield) as trifluoroacetic acid salts. MS (ESI) m/e 447 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 0.94 (d, J=6.41 Hz, 4H) 1.35-1.53 (m, 4H) 1.99-2.11 (m, 4H) 2.50-2.57 (m, 1H) 3.15-3.25 (m, 1H) 3.71-3.82 (m, 1H) 6.66-6.79 (m, 1H) 7.08 (s, 1H) 7.18 (dd, J=7.93, 4.58 Hz, 1H) 8.29 (dd, J=4.73, 1.68 Hz, 1H) 8.35 (s, 1H) 8.79 (d, J=7.02 Hz, 1H) 12.03 (s, 1H).

Workup

  1. concentrationconcentrated 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-7a11f863f40d4033b3db100d2589c5cd
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Reaction notes

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