2,4,6-Trimethylaniline → HCID 44308664, compound

HRID 2417298Notes

Reaction equation

HRID 2417298 reaction equation
C(N(C(C)C)CC)(C)C.C(OC(O[NH:18][C:19]1[S:20][C:21]2[CH:27]=[C:26]([C:28]([OH:30])=O)[C:25]([Cl:31])=[CH:24][C:22]=2[N:23]=1)=O)(C)(C)C.[C:32]([O:36][C:37](ONC1SC2C(Cl)=C(C(O)=O)C=CC=2N=1)=[O:38])([CH3:35])([CH3:34])[CH3:33].[CH3:54][C:55]1[CH:61]=[C:60]([CH3:62])[CH:59]=[C:58]([CH3:63])[C:56]=1[NH2:57].CN([P+](ON1N=NC2C1=CC=CC=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C)C=O.CCOC(C)=O.O>[Cl:31][C:25]1[C:26]([C:28]([NH:57][C:56]2[C:58]([CH3:63])=[CH:59][C:60]([CH3:62])=[CH:61][C:55]=2[CH3:54])=[O:30])=[CH:27][C:21]2[S:20][C:19]([NH:18][C:37](=[O:38])[O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[N:23][C:22]=2[CH:24]=1

Participants

10

Reactant 5

HCID 69132,4,6-Trimethylaniline2×HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 22634423HCID 22634423, compoundHCID 22634527HCID 22634527, compound

Product 1

HCID 44308664HCID 44308664, compoundYield 10%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diisopropylethyl amine (400 μL, 2.2 mmol) was added to a stirred suspension of compounds 179C and 180C (328 mg, 1 mmol), 2,4,6-trimethylaniline (170 μL, 1.1 mmol) and benzotriazolo-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (Castro's reagent, 485 mg, 1.1 mmol) in dichloromethane (5 mL). The solution was stirred at RT for 18 h, filtered and dried to obtain a mixture of intermediate benzotriazolo-esters (400 mg) which was dissolved in dimethylformamide (5 mL) and 2,4,6-trimethylaniline (560 μL, 4 mmol) was added. The solution was heated to 50° C. for 72 h, cooled and diluted with EtOAc (100 mL) and water (100 mL). The EtOAc layer was separated, washed with 1 N aq. HCl solution (100 mL, 3×), brine (50 mL), dried (MgSO4), filtered and concentrated. The orange-yellow solid was dissolved in dimethylsulfoxide (1 mL) and diluted with methanol (5 mL), followed by water (5 mL). The solution was let stand at RT for several hours. The precipitated solid was filtered, washed with water (20 mL), dried and then recrystallized from DMSO—MeOH—H2O mixture to obtain the pure title compound 179D (45 mg, 10%).

Workup

  1. filtrationfiltered
  2. customdried
  3. customto obtain
  4. temperatureThe solution was heated to 50° C. for 72 h
  5. temperaturecooled
  6. customThe EtOAc layer was separated
  7. washwashed with 1 N aq. HCl solution (100 mL, 3×), brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. dissolutionThe orange-yellow solid was dissolved in dimethylsulfoxide (1 mL)
  12. additiondiluted with methanol (5 mL)
  13. customat RT
  14. customfor several hours
  15. filtrationThe precipitated solid was filtered
  16. washwashed with water (20 mL)
  17. customdried
  18. customrecrystallized from DMSO—MeOH—H2O mixture

Sources & evidence

ORD record
ord-194cff05d0dc490a8edfa3f43efe654b
Source dataset
uspto-grants-2004_11
Patent number
US06825355B2

Reaction notes

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