3,4-Dimethylbenzoic acid → HCID 57345465, compound

HRID 1808838Notes

Reaction equation

HRID 1808838 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:43][NH:44][C@@H:45]([CH2:52][CH2:53][CH3:54])[CH2:46][N:47]1[CH2:50][CH:49]([OH:51])[CH2:48]1>C(Cl)Cl>[OH:51][CH:49]1[CH2:48][N:47]([CH2:46][C@@H:45]([N:44]([CH3:43])[C:5](=[O:7])[C:4]2[CH:8]=[CH:9][C:10]([CH3:11])=[C:2]([CH3:1])[CH:3]=2)[CH2:52][CH2:53][CH3:54])[CH2:50]1

Participants

6

Reactant 4

HCID 120733,4-Dimethylbenzoic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67775012HCID 67775012, compound

Product 1

HCID 57345465HCID 57345465, compoundYield 27.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3,4-Dimethylbenzoic acid (0.174 g, 1.16 mmol), TBTU (0.373 g, 1.16 mmol) and DIPEA (0.303 mL, 1.74 mmol) was stirred in DCM (2 mL) for 40 min before (S)-1-(2-(methylamino)pentyl)azetidin-3-ol (Compound J4) (0.1 g, 0.58 mmol) was added. The resultant mixture was stirred at rt overnight. The solvent was removed under reduced pressure and the residue dissolved in a mixture of MeOH (3 mL) and NaOH (aq. 1 mL, 1M). The resultant mixture was stirred at rt for 90 min before the MeOH was removed on a vacuum centrifuge. The crude product was extracted with DCM and concentrated under reduced pressure. To the residue was DMSO (1 mL), DCM (3 mL) and KOH (1M solution, 3 mL) added. The organic phase was filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC. The product containing fractions was concentrated, water (5 mL) and DCM (5 mL) was added and the pH was adjusted to 12 using KOH (1M solution). The organic layer was filtered through a phase separator and the solvent was removed under reduced pressure to give the title compound (48 mg, 27%). Mixture of rotamers: (600 MHz, DMSO-d6) δ 0.69-0.78, 0.85-0.93, 0.94-1.06, 1.08-1.50, 2.19-2.28, 2.32-2.41, 2.44-2.56, 2.56-2.65, 2.66-2.76, 3.27-3.38, 3.43-3.55, 4.03-4.20, 4.44-4.52, 5.17-5.26, 6.97-7.21. Total no of protons: 28. HRMS (M+H)+: calculated 305.2229. found 305.2214.

Workup

  1. additionwas added
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue dissolved in a mixture of MeOH (3 mL) and NaOH (aq. 1 mL, 1M)
  4. customwas removed on a vacuum centrifuge
  5. extractionThe crude product was extracted with DCM
  6. concentrationconcentrated under reduced pressure
  7. additionadded
  8. filtrationThe organic phase was filtered through a phase separator
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by preparative HPLC
  11. additionThe product containing fractions
  12. concentrationwas concentrated
  13. additionwater (5 mL) and DCM (5 mL) was added
  14. filtrationThe organic layer was filtered through a phase separator
  15. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-390ed4913a50415fb038494f615625e7
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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