Sodium borohydride → HCID 10436965, compound

HRID 861007Notes

Reaction equation

HRID 861007 reaction equation
C(O[C:4](=[O:38])[C:5]([F:37])([F:36])[S:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]([C:29]([S:32]([CH3:35])(=[O:34])=[O:33])([CH3:31])[CH3:30])[CH:22]=[C:23]4[C:28]=3[N:27]=[CH:26][CH:25]=[CH:24]4)[CH:14]=2)[CH:12]=1)C.[CH3:39][Mg+].[Br-].[BH4-].[Na+]>C(Cl)Cl.[NH4+].[Cl-]>[F:36][C:5]([F:37])([S:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]([C:29]([S:32]([CH3:35])(=[O:34])=[O:33])([CH3:30])[CH3:31])[CH:22]=[C:23]4[C:28]=3[N:27]=[CH:26][CH:25]=[CH:24]4)[CH:14]=2)[CH:12]=1)[CH:4]([OH:38])[CH3:39]

Participants

6

Reactant 3

HCID 4311764Sodium borohydrideHCID 69374948HCID 69374948, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 10436965HCID 10436965, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent2×

Procedure

To a solution of difluoro-(5-{3-[6-(1-methanesulfonyl-1-methyl-ethyl)-quinolin-8-yl]-phenyl}-pyridin-3-ylsulfanyl)-acetic acid ethyl ester from Step 1 (1.0 eq.) in CH2Cl2 (0.2M) at −78° C. was added MeMgBr (3.0 eq.; 3.0M in Et2O). The mixture was warmed to rt, stirred for 12 h, poured in saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was dissolved in EtOH (0.2M) then NaBH4 (3.0 eq.) was added. The mixture was stirred for 2 h, poured in saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography (Hex:EtOAc; 1:9) afforded the title compound as a white solid. 1H NMR (400 MHz, acetone-d6): δ 9.04 (d, 1H), 8.97 (dd, 1H), 8.75 (d, 1H), 8.50 (dd, 1H), 8.35–8.34 (m, 2H), 8.26 (d, 1H), 8.13 (s, 1H), 7.85 (dt, 1H), 7.82 (dt, 1H), 7.68 (t, 1H), 7.61 (dd, 1H), 5.15 (d, 1H), 4.20 (m, 1H), 2.76 (s, 3H), 2.03 (s, 6H), 1.37 (d, 3H).

Workup

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in EtOH (0.2M)
  7. stirringThe mixture was stirred for 2 h
  8. extractionextracted with EtOAc (2×)
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-955bc16ddf28410c8d9e47a14887e4bc
Source dataset
uspto-grants-2006_12
Patent number
US07153968B2

Reaction notes

Loading…