Hydrochloric Acid → HCID 135956077, compound

HRID 2075755Notes

Reaction equation

HRID 2075755 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14](=[O:38])[NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[C:23][C:24]2[C:25]([C:30]3[CH:35]=[C:34]([CH3:36])[CH:33]=[CH:32][C:31]=3[OH:37])=[N:26][N:27]([CH3:29])[CH:28]=2)=[CH:18][CH:17]=1)=O)(C)(C)C.Cl.[S:40]1[CH:44]=[CH:43][CH:42]=[C:41]1[S:45](Cl)(=[O:47])=[O:46].C(N(CC)CC)C>C1COCC1.O1CCOCC1.ClCCl>[OH:37][C:31]1[CH:32]=[CH:33][C:34]([CH3:36])=[CH:35][C:30]=1[C:25]1[C:24]([C:23]#[C:22][C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:14]([CH:9]3[CH2:10][CH2:11][CH2:12][CH2:13][N:8]3[S:45]([C:41]3[S:40][CH:44]=[CH:43][CH:42]=3)(=[O:47])=[O:46])=[O:38])=[CH:21][CH:20]=2)=[CH:28][N:27]([CH3:29])[N:26]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 855182-Thiophenesulfonyl chlorideHCID 135974936HCID 135974936, compound2×

Product 1

HCID 135956077HCID 135956077, compoundYield 62.4%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of compound 3 (8.72 g, 16.95 mmol) in THF (100 mL) was added a solution of 4 M HCl in dioxane (200 mL). The reaction mixture was stirred at rt and monitored with TLC and LC-MS. When all the starting material 3 was reacted, the reaction mixture was concentrated to dryness. 2-Thiophenesulfonyl chloride (3.10 g, 16.95 mmol) and dry dichloromethane (˜200 mL) were added to above residua. Triethylamine (12.0 mL, 86.1 mmol) was then slowly added to above mixture while cooling with an ice-water bath. The final mixture was stirred at rt overnight. It was then washed with brine, and dried over sodium sulfate. After filtration, the filtrate was concentrated and purified with silica column chromatography eluting with dichloromethane-ethyl acetate (v/v 9/1), then hexanes-ethyl acetate (v/v 1/1). The product was recrystallized from hot methanol to give the title compound (23, 5.93 g) as light yellow solid in 62.4% yield. 1H NMR (CDCl3, 500 MHz) δ 10.48 (s, 1H), 8.45 (s, 1H), 8.41 (s, 1H), 7.67 (m, 2H), 7.61 (s, 1H), 7.58 (d, 2H, J=8.0 Hz), 7.50 (d, 2H, J=8.5 Hz), 7.14 (t, 1H, J=4.0 Hz), 7.07 (d, 1H, J=8.0 Hz), 6.94 (d, 1H, J=8.0 Hz), 4.66 (d, 1H, J=5.0 Hz), 4.07 (br d, 1H, J=13.5 Hz), 3.93 (s, 3H), 3.17 (t, 1H, J=13.0 Hz), 2.36 (m, 1H), 2.34 (s, 3H), 1.67-1.45 (m, 3H), 1.29 (m, 2H). LCMS (ESI) m/z 561.14 (MH+, 100); HPLC: tR=5.82 min.

Workup

  1. concentrationthe reaction mixture was concentrated to dryness
  2. temperaturewhile cooling with an ice-water bath
  3. washIt was then washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated
  7. custompurified with silica column chromatography
  8. washeluting with dichloromethane-ethyl acetate (v/v 9/1)
  9. customThe product was recrystallized from hot methanol

Sources & evidence

ORD record
ord-b5591896c1fc40a78edc69626cf7e1f9
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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