Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → HCID 71599792, compound

HRID 75571Notes

Reaction equation

HRID 75571 reaction equation
C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[C:18]([C:22]1[CH:23]=[C:24]([NH:43][C:44]([NH:46][C@@H:47]2[C:56]3[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=3)[C@H:50]([O:57][C:58]3[CH:59]=[CH:60][C:61]4[N:62]([C:64]([CH:67]([CH3:69])[CH3:68])=[N:65][N:66]=4)[CH:63]=3)[CH2:49][CH2:48]2)=[O:45])[N:25]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH2:34][CH2:35][O:36]C3CCCCO3)[CH:28]=2)[N:26]=1)([CH3:21])([CH3:20])[CH3:19]>CO>[C:18]([C:22]1[CH:23]=[C:24]([NH:43][C:44]([NH:46][C@@H:47]2[C:56]3[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=3)[C@H:50]([O:57][C:58]3[CH:59]=[CH:60][C:61]4[N:62]([C:64]([CH:67]([CH3:69])[CH3:68])=[N:65][N:66]=4)[CH:63]=3)[CH2:49][CH2:48]2)=[O:45])[N:25]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH2:34][CH2:35][OH:36])[CH:28]=2)[N:26]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

4

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)2×HCID 86686680HCID 86686680, compound

Product 1

HCID 71599792HCID 71599792, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
55 °C

Procedure

Pyridinium para-toluene sulfonate (44.0 mg, 0.17 mmol) was added to Intermediate 4c (124 mg, 0.17 mmol) in MeOH (3.0 mL). After 2 h, further pyridinium para-toluene sulfonate (100 mg, 0.39 mmol) was added, and the reaction stirred for 12 h. The reaction was then heated to 55° C. for 2 h, then cooled, and the solvent volume reduced to approximately ⅓ of its volume in vacuo. The residue was partitioned between EtOAc (50 mL) and saturated NaHCO3 (50 mL). The aqueous layer was extracted into EtOAc (3×), then the combined organic layers washed with brine, dried (MgSO4) and evaporated in vacuo. The product was purified by FCC, using 0-10% MeOH in DCM, then further purified by HPLC (C18 X-select column, 10-98% MeCN in H2O, 0.1% formic acid) to give the title compound (50.0 mg, 0.08 mmol, 47%). LCMS (Method 5): Rt 4.04 mins, m/z 624 [MH+]. 1H NMR (400 MHz, CDCl3): 1.30 (9H, s), 1.40-1.44 (3H, d, J=6.9 Hz), 1.44-1.47 (3H, d, J=6.9 Hz), 1.84-1.98 (1H, m), 2.00-2.10 (2H, m), 2.18-2.26 (1H, m), 3.16-3.26 (1H, sp, J=6.9 Hz), 3.87-3.92 (2H, m), 4.03-4.07 (2H, m), 5.01-5.09 (1H, td, J 8.9, 5.3 Hz), 5.14-5.17 (1H, t, J=4.0 Hz), 5.47-5.52 (1H, br d, J=8.7 Hz), 6.29 (1H, s) 6.60 (1H, br s), 6.80-6.84 (1H, m), 6.96-7.00 (1H, dd, J 9.9, 2.1 Hz), 7.07-7.11 (2H, m), 7.23-7.30 (5H, m), 7.38-7.40 (1H, d, J=1.6 Hz), 7.53-7.57 (1H, d, J=9.9 Hz).

Workup

  1. temperaturecooled
  2. customThe residue was partitioned between EtOAc (50 mL) and saturated NaHCO3 (50 mL)
  3. extractionThe aqueous layer was extracted into EtOAc (3×)
  4. washthe combined organic layers washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe product was purified by FCC
  8. customfurther purified by HPLC (C18 X-select column, 10-98% MeCN in H2O, 0.1% formic acid)

Sources & evidence

ORD record
ord-460caef7c0a34e299a8f7f0e707402ee
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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