Diisopropylethylamine → HCID 59544176, compound

HRID 2425575Notes

Reaction equation

HRID 2425575 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:13]([OH:15])=O)[CH:9]=2)[N:4]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[CH3:53][N:54]1[C:58]([CH3:59])=[C:57]([C@H:60]([NH2:62])[CH3:61])[CH:56]=[N:55]1>C(Cl)Cl>[CH3:53][N:54]1[C:58]([CH3:59])=[C:57]([C@H:60]([NH:62][C:13]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]=[C:3]([C:2]([F:1])([F:17])[F:16])[CH:12]=[CH:11]3)=[O:15])[CH3:61])[CH:56]=[N:55]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450732972-(Trifluoromethyl)quinoline-6-carboxylic acidHCID 67180429HCID 67180429, compound

Product 1

HCID 59544176HCID 59544176, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Trifluoromethylquinoline-6-carboxylic acid (100 mg, 0.415 mmol) was dissolved in DCM (10 mL) and N,N-di-iso-propylethylamine (Hunig's base, 268 μl, 1.54 mmol) was added. HATU (158 mg, 0.415 mmol) was added followed by (1R)-1-[1,5-dimethyl-1H-pyrazol-4-yl]ethanamine dihydrochloride (88 mg, 0.415 mmol) and the solution was stirred at RT overnight. The reaction mixture was concentrated and the residue was dissolved in EtOAc (65 mL) then partitioned with sat. aq. NaHCO3 (2×20 mL) and then brine (30 mL). The organic layer dried over MgSO4, filtered and solvent removed under reduced pressure to give a golden oil/gum. The product was purified using an ISCO (12 g column), eluting with EtOAc:Heptane (5:95 increasing to 100:0). Fractions containing pure product concentrated under reduced pressure to give a white foamy solid, 150 mg, yield=41%. 1H NMR (400 MHz, CD3OD) δ 8.68 (1H, d), 8.47-8.49 (1H, m), 8.20-8.23 (2H, m), 7.92 (1H, d), 7.48 (1H, s), 5.29 (1H, q) 3.76 (3H, s), 2.33 (3H, s) and 1.61 (3H, d). LCMS (2 min run): UV (1.37 min, 82%); ELSD (1.37 min, 100%). Mass ion: 363=MH+

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in EtOAc (65 mL)
  3. customthen partitioned with sat. aq. NaHCO3 (2×20 mL)
  4. dry with materialThe organic layer dried over MgSO4
  5. filtrationfiltered
  6. customsolvent removed under reduced pressure
  7. customto give a golden oil/gum
  8. customThe product was purified
  9. washeluting with EtOAc:Heptane (5:95 increasing to 100:0)
  10. additionFractions containing pure product
  11. concentrationconcentrated under reduced pressure
  12. customto give a white foamy solid, 150 mg, yield=41%
  13. customLCMS (2 min run)
  14. customUV (1.37 min, 82%)
  15. customELSD (1.37 min, 100%)

Sources & evidence

ORD record
ord-27dc51e8814d4a278a33c9cc0fcdca53
Source dataset
uspto-grants-2011_06
Patent number
US07964732B2

Reaction notes

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