Dimethyl Sulfoxide → HCID 54336098, compound

HRID 1419703Notes

Reaction equation

HRID 1419703 reaction equation
CS(C)=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[C:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[S:27][C:28]([C:32]([N:34]([C@H:38]([CH3:55])[C@:39]([C:47]3[CH:52]=[CH:51][C:50]([F:53])=[CH:49][C:48]=3[F:54])([OH:46])[CH2:40][N:41]3[CH:45]=[N:44][CH:43]=[N:42]3)[CH2:35][CH2:36][OH:37])=[O:33])=[C:29]([CH3:31])[N:30]=2)=[CH:22][CH:21]=1)#[N:19].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:54][C:48]1[CH:49]=[C:50]([F:53])[CH:51]=[CH:52][C:47]=1[C@:39]1([CH2:40][N:41]2[CH:45]=[N:44][CH:43]=[N:42]2)[O:46][CH:36]([OH:37])[CH2:35][N:34]([C:32]([C:28]2[S:27][C:26]([C:23]3[CH:24]=[CH:25][C:20]([C:18]#[N:19])=[CH:21][CH:22]=3)=[N:30][C:29]=2[CH3:31])=[O:33])[C@@H:38]1[CH3:55]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 516892Sodium BicarbonateHCID 54141090HCID 54141090, compound

Product 1

HCID 54336098HCID 54336098, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-40 °C

Procedure

To a cooled (-78° C.) solution of DMSO (0.29 mL, 4.17 mmol) in CH2Cl2 (10 mL) was added a solution of trifluoroacetic anhydride (0.30 mL, 2.09 mmol) in CH2Cl2 (1 mL) dropwise. After ten minutes, a solution of (1R,2R)-2-(4-cyanophenyl)-N-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-N-(2-hydroxyethyl)-4-methylthiazole-5-carboxamide (0.9 g, 1.67 mmol, obtained in example 82) in CH2Cl2 (3 mL) was added. The mixture was stirred for 1 h, and then triethylamine (1.1 mL, 8.3 mmol) was added. The reaction mixture was allowed to warm up to -40° C. and was stirred at this temperature for 1.5 h and then at -10° C. for 30 min. 10% aqueous NaHCO3 solution was added, the organic phase was separated and the aqueous phase was extracted with chloroform. The combined organic extracts were washed with water, dried over anhydrous Na2SO4, filtered and concentrated to a crude product. Purification by flash chromatography afforded the title compound as a white solid: mp 225°-228° C.; 1H NMR (300 MHz, CDCl3) δ (TMS) 8.06 and 8.05 (d, J=8.4, 2H, arom), 7.77 (s, 1H, triazole), 7.76 (d, J=8.4, 2H, arom), 7.35 (dt, Jd =6.5, Jt =8.8, 1H, arom), 7.30 (s, 1H, triazole), 7.0-6.7 (m, 2H, arom), 5.83 (m, 1H, OCHOH), 5.8-3.2 (several broad signals), 2.57 and 2.55 (s, 3H, Me-thiazole), 1.14 (d, J=6.8, 3H, MeCH); [α]D =-79.8° (c 1, CHCl3). Analysis calculated for C26H22F2N6O3S.1/2H2O: C 57.24; H 4.21; N 15.40; S 5.86. Found: C 57.49; H 4.03; N 15.08; S 5.69.

Workup

  1. waitAfter ten minutes
  2. stirringwas stirred at this temperature for 1.5 h
  3. waitat -10° C. for 30 min
  4. customthe organic phase was separated
  5. extractionthe aqueous phase was extracted with chloroform
  6. washThe combined organic extracts were washed with water
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a crude product
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-602b43ca58d24feca517283e56b471a5
Source dataset
uspto-grants-1999_03
Patent number
US05888941

Reaction notes

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