Butyric Acid → HCID 57489439, compound

HRID 1961535Notes

Reaction equation

HRID 1961535 reaction equation
[C:1]([OH:6])(=O)[CH2:2][CH2:3][CH3:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.Cl.[Cl:39][C:40]1[CH:41]=[C:42]([C:48]2([C:64]([F:67])([F:66])[F:65])[O:52][N:51]=[C:50]([C:53]3[CH:58]=[CH:57][C:56]([C:59]4([F:63])[CH2:62][NH:61][CH2:60]4)=[CH:55][CH:54]=3)[CH2:49]2)[CH:43]=[C:44]([Cl:47])[C:45]=1[F:46]>CN(C=O)C>[Cl:39][C:40]1[CH:41]=[C:42]([C:48]2([C:64]([F:65])([F:66])[F:67])[O:52][N:51]=[C:50]([C:53]3[CH:58]=[CH:57][C:56]([C:59]4([F:63])[CH2:62][N:61]([C:1](=[O:6])[CH2:2][CH2:3][CH3:4])[CH2:60]4)=[CH:55][CH:54]=3)[CH2:49]2)[CH:43]=[C:44]([Cl:47])[C:45]=1[F:46]

Participants

6

Reactant 4

HCID 264Butyric AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86661736HCID 86661736, compound

Product 1

HCID 57489439HCID 57489439, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of butyric acid (50 mg) in DMF (5 mL) was added HATU (200 mg) then triethyl amine (150 μL). The resulting solution was stirred at ambient temperature for 15 minutes then 5-(3,5-dichloro-4-fluorophenyl)-3-(4-(3-fluoroazetidin-3-yl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole hydrochloride (Preparation 16 100 mg) was added in one portion. Reaction stirred at ambient temperature for 16 hours. Solvent was removed in vacuo and the residue partitioned between water (10 mL) and CH2Cl2 (10 mL). Organic phase collected and condensed. The crude material was adsorbed on silica and chromatographed on a 12 g silica column, eluting with a gradient of 0% to 100% ethyl acetate in heptane. Fractions containing the desired material were combined and concentrated. Et2O (˜½ mL) was added to the resulting film. Placing the flask on high vacuum overnight resulted in formation of a white foam. Yield 86 mg (80%). 1H NMR (CDCl3) δ 7.75 (d, 2H), 7.61 (d, 2H), 7.55 (d, 2H), 4.68-4.33 (m, 4H), 4.12 (d, 1H), 3.72 (d, 1H), 2.19 (m, 2H), 1.73 (m, 2H), 1.01 (m, 3H). LC/MS retention time=3.688 minutes, MS calculated for (C23H19Cl2F5N2O2), 520.07; found 521.0 M+H.

Workup

  1. customReaction
  2. stirringstirred at ambient temperature for 16 hours
  3. customSolvent was removed in vacuo
  4. customthe residue partitioned between water (10 mL) and CH2Cl2 (10 mL)
  5. customOrganic phase collected
  6. customcondensed
  7. customchromatographed on a 12 g silica column
  8. washeluting with a gradient of 0% to 100% ethyl acetate in heptane
  9. additionFractions containing the desired material
  10. concentrationconcentrated
  11. additionEt2O (˜½ mL) was added to the resulting film
  12. customon high vacuum overnight
  13. customresulted in formation of a white foam

Sources & evidence

ORD record
ord-ffc5325db725471fba50cb5ac4997b8d
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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