Diisopropylethylamine → HCID 58133387, compound

HRID 1042315Notes

Reaction equation

HRID 1042315 reaction equation
[Br:1][C:2]1[C:3]([Cl:26])=[C:4]([C:9]2[C:10]([OH:25])=[N:11][C:12]3[C:17]([C:18]=2[O:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])=[CH:16][CH:15]=[CH:14][N:13]=3)[C:5]([F:8])=[CH:6][CH:7]=1.C(N(CC)C(C)C)(C)C.[F:36][CH:37]([F:47])[CH2:38]OS(C(F)(F)F)(=O)=O>C(#N)C>[Br:1][C:2]1[C:3]([Cl:26])=[C:4]([C:9]2[C:10](=[O:25])[N:11]([CH2:38][CH:37]([F:47])[F:36])[C:12]3[C:17]([C:18]=2[O:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])=[CH:16][CH:15]=[CH:14][N:13]=3)[C:5]([F:8])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 27740892,2-Difluoroethyl trifluoromethanesulfonate3×HCID 178454612HCID 178454612, compound

Product 1

HCID 58133387HCID 58133387, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of Isobutyric acid 3-(3-bromo-2-chloro-6-fluoro-phenyl)-2-hydroxy-[1,8]naphthyridin-4-yl ester (1.749 g) in acetonitrile (17 ml) was added N,N-diisopropylethylamine (“Hunig's base”) (0.83 ml) at ambient temperature. The mixture was stirred for 5 minutes at ambient temperature before drop wise addition of a solution of 2,2-difluoroethyltrifluoromethanesulfonate (1.022 g) at ambient temperature. The reaction mixture was stirred at ambient temperature for 7 hours when further 2,2-difluoroethyltrifluoromethanesulfonate (0.5 g) and the reaction was stirred overnight. A further portion of 2,2-difluoroethyltrifluoromethanesulfonate (0.5 g) and N,N-diisopropylethylamine (“Hunig's base”) (0.83 ml) was added and the reaction was stirred for 5 hours then left to stand overnight. The reaction was concentrated and partitioned between ethyl acetate and 2M hydrochloric acid. The organic layer was dried and concentrated and the oily residue was purified by column chromatography on silica (eluent: 4:1 hexane:ethyl acetate) to give Compound No. D23 of Table D as a light yellow solid (1.56 g).

Workup

  1. stirringthe reaction was stirred for 5 hours
  2. waitthen left
  3. waitto stand overnight
  4. concentrationThe reaction was concentrated
  5. custompartitioned between ethyl acetate and 2M hydrochloric acid
  6. customThe organic layer was dried
  7. concentrationconcentrated
  8. customthe oily residue was purified by column chromatography on silica (eluent: 4:1 hexane:ethyl acetate)
  9. customto give Compound No

Sources & evidence

ORD record
ord-d2f0811f4f564d0d823fac9dc5a35199
Source dataset
uspto-grants-2013_10
Patent number
US08557840B2

Reaction notes

Loading…