Diisopropylethylamine → HCID 76282857, compound

HRID 624987Notes

Reaction equation

HRID 624987 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)[CH2:3][CH2:2]1.Cl.[O:22]=[S:23]1(=[O:31])[CH2:27][CH:26]([C:28]([NH2:30])=[O:29])[NH:25][CH2:24]1.F[B-](F)(F)F.BrC1C=CC=C[N+]=1CC.CCN(C(C)C)C(C)C>C1COCC1>[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([N:25]3[CH:26]([C:28]([NH2:30])=[O:29])[CH2:27][S:23](=[O:31])(=[O:22])[CH2:24]3)=[O:14])[CH:9]=[CH:8][C:7]=2[N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27363002-Bromo-1-ethylpyridinium tetrafluoroborateHCID 710872926-(Cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)picolinic acidHCID 902038431,1-Dioxo-1,3-thiazolidine-4-carboxamide hydrochloride

Product 1

HCID 76282857HCID 76282857, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (Example 1 b, 200 mg, 704 μmol), 1,1-dioxo-1,3-thiazolidine-4-carboxamide hydrochloride (Example 127 d, 169 mg, 844 μmol), 2-bromo-1-ethylpyridinium tetrafluoroborate (212 mg, 774 μmol) and DIEA (273 mg, 361 μL, 2.11 mmol) in THF (20 mL) was stirred for 24 h at ambient temperature. The solvent was removed under reduced pressure, ice/sat. aqueous NaHCO3 (75 mL) and EtOAc (75 mL) were added and the layers were separated. The aqueous layer was extracted with EtOAc (75 mL). The combined extracts were washed with ice/0.1N HCl (75 mL) and ice/brine (75 mL), dried over Na2SO4 and filtered. The solvent was removed under reduced pressure to give a yellow solid which was recrystallized from EtOAc (3 mL). The crude product was purified by chiral HPLC (Reprosil Chiral NR, EtOH/heptane 40%/60%) to give the title compound (63 mg, 21%) as colorless oil, MS (EI): m/e=431.3 [MH+].

Workup

  1. customwas stirred for 24 h at ambient temperature
  2. customThe solvent was removed under reduced pressure, ice/
  3. additionaqueous NaHCO3 (75 mL) and EtOAc (75 mL) were added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with EtOAc (75 mL)
  6. washThe combined extracts were washed with ice/0.1N HCl (75 mL) and ice/brine (75 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe solvent was removed under reduced pressure
  10. customto give a yellow solid which
  11. customwas recrystallized from EtOAc (3 mL)
  12. customThe crude product was purified by chiral HPLC (Reprosil Chiral NR, EtOH/heptane 40%/60%)

Sources & evidence

ORD record
ord-7f8e88dfd0184b13b8ebf05618e6c3f3
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Reaction notes

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