Trifluoroacetic acid → HCID 72205743, compound

HRID 1520793Notes

Reaction equation

HRID 1520793 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2([C:33]([F:36])([F:35])[F:34])[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4([F:32])[CH2:31][NH:30][CH2:29]4)=[CH:24][CH:23]=3)[O:18]2)[CH:12]=[C:13]([Cl:16])[C:14]=1[F:15].C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:66][S:67]([CH2:70][C:71](O)=[O:72])(=[O:69])=[O:68]>CN(C=O)C>[Cl:16][C:13]1[CH:12]=[C:11]([C:17]2([C:33]([F:34])([F:35])[F:36])[O:21][N:20]=[C:19]([C:22]3[CH:23]=[CH:24][C:25]([C:28]4([F:32])[CH2:31][N:30]([C:71](=[O:72])[CH2:70][S:67]([CH3:66])(=[O:69])=[O:68])[CH2:29]4)=[CH:26][CH:27]=3)[O:18]2)[CH:10]=[C:9]([Cl:8])[C:14]=1[F:15]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 37328412-Methanesulfonylacetic acidHCID 90013618HCID 90013618, compound

Product 1

HCID 72205743HCID 72205743, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of trifluoroacetic acid salt of 5-(3,5-dichloro-4-fluoro-phenyl)-3-[4-(3-fluoro-azetidin-3-yl)-phenyl]-5-trifluoromethyl-[1,4,2]dioxazole (0.35 g, 0.77 mmol, 1 eq) in DMF (5 mL) was added triethyl amine (0.867 mL, 6.178 mmol, 8 eq.), followed by addition of EDC.HCl (0.22 g, 1.15 mmol, 1.5 eq), HOBt (0.104 g, 0.77 mmol, 1 eq) and methanesulfonyl-acetic acid (0.213 g, 1.54 mmol, 2 eq) at room temperature. Resulting reaction mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched by water (50 mL) and extracted with ethyl acetate (3×30 mL). Combined organic phase was washed with saturated solution of LiCl solution (30 mL), brine (30 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown thick oil (0.51 g, Crude). Crude was purified by combiflash using 40 g Redisep column. Desired compound was eluted in 47% ethyl acetate in hexane to afford title compound as off white solid (0.225 g, 50.82%). 1H NMR (400 MHz, CDCl3) δ: 3.17 (s, 3H), 3.87 (s, 2H), 4.37-4.45 (m, 1H), 4.52-4.60 (m, 1H), 4.80 (d, J=19.64 Hz, 2H), 7.61-7.65 (m, 4H), 7.91 (d, J=8.24 Hz, 2H), LC-MS (m/z): 571.0 (M−H), HPLC Purity: 93.59%.

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. customwas quenched by water (50 mL)
  5. extractionextracted with ethyl acetate (3×30 mL)
  6. washCombined organic phase was washed with saturated solution of LiCl solution (30 mL), brine (30 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto get brown thick oil (0.51 g, Crude)
  10. customCrude was purified by combiflash
  11. washDesired compound was eluted in 47% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9e1924091f054b84b923d58fa1c9d165
Source dataset
uspto-grants-2015_07
Patent number
US09073912B2

Reaction notes

Loading…