p-Toluenesulfonic acid → HCID 131736625, compound

HRID 1481295Notes

Reaction equation

HRID 1481295 reaction equation
[CH3:1][C@H:2]([CH:30]=C)[C:3]([NH:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[CH:16][N:15]=[C:14]([C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:19][CH:20]=C)[CH:13]=1)=[O:4].CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[CH3:30][C@H:2]1[C:3](=[O:4])[NH:5][C:6]2[CH:7]=[N:8][CH:9]=[CH:10][C:11]=2[C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH:13]=2)[C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])[CH2:19][CH:20]=[CH:1]1

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 131736626HCID 131736626, compound

Product 1

HCID 131736625HCID 131736625, compoundYield 7.3%

Reagents, catalysts & solvents 2

HCID 178425456HCID 178425456, compoundCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of 72D (220 mg, 0.521 mmol), pTsOH (194 mg, 1.020 mmol) in CH2Cl2 (100 mL) was degassed by bubbling Ar through for 10 mins and heated at 40° C. for 10 mins. Then, Grubbs II (190 mg, 0.224 mmol) in 3 ml Ar degassed DCM was added dropwise via a syringe pump under Ar, heated at 40° C. for a total of 24 hrs. The reaction mixture was neutralized with sat. aq. NaHCO3 and the organic phase separated and washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by prep HPLC and the desired fractions neutralized with conc. NaHCO3, concentrated to small volume, extracted with EtOAc, dried over MgSO4, filtered and concentrated to yield the desired product as a white solid (15 mg, 7.3%). 1H NMR (400 MHz, METHANOL-d4) δ 8.65 (dd, J=11.4, 5.1 Hz, 2H), 8.54 (s, 1H), 7.60 (d, J=5.1 Hz, 1H), 7.37 (dd, J=5.1, 1.5 Hz, 1H), 6.99 (s, 1H), 5.76 (ddd, J=15.3, 10.6, 4.7 Hz, 1H), 4.68 (dd, J=11.2, 3.5 Hz, 1H), 4.41 (dd, J=15.2, 9.5 Hz, 1H), 3.18 (dq, J=9.3, 6.7 Hz, 1H), 2.78 (ddd, J=8.4, 7.3, 3.9 Hz, 1H), 2.04 (q, J=11.4 Hz, 1H), 1.47 (s, 9H), 1.10 (d, J=6.8 Hz, 3H).

Workup

  1. customby bubbling Ar through for 10 mins
  2. additionwas added dropwise via a syringe pump under Ar
  3. temperatureheated at 40° C. for a total of 24 hrs
  4. customthe organic phase separated
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by prep HPLC
  10. concentrationconcentrated to small volume
  11. extractionextracted with EtOAc
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-c89ff0e0ef25482086f573fd903d721b
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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