Dimethyl Sulfoxide → HCID 73553419, compound

HRID 2191375Notes

Reaction equation

HRID 2191375 reaction equation
C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.CS(C)=O.[Cl:18][C:19]1[C:20]([NH:25][CH2:26][C@H:27]([C@H:29]2[C@H:36]3[C@H:32]([O:33][C:34]([CH3:38])([CH3:37])[O:35]3)[C:31]([CH2:39][O:40][C:41]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[CH:30]2)[OH:28])=[N:21][CH:22]=[CH:23][N:24]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:18][C:19]1[C:20]([NH:25][CH2:26][C:27]([C@H:29]2[C@H:36]3[C@H:32]([O:33][C:34]([CH3:38])([CH3:37])[O:35]3)[C:31]([CH2:39][O:40][C:41]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[CH:30]2)=[O:28])=[N:21][CH:22]=[CH:23][N:24]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 86648185HCID 86648185, compound

Product 1

HCID 73553419HCID 73553419, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

TFAA (0.459 mL, 3.25 mmol, 3.2 equiv) in DCM (0.5 mL) was added dropwise to DMSO (0.303 mL, 4.26 mmol, 4.2 equiv) in DCM (0.5 mL) at −78° C. After 30 minutes, (S)-2-(3-chloropyrazin-2-ylamino)-1-((3aS,4S,6aR)-2,2-dimethyl-6-(trityloxymethyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)ethanol (1-6) (593 mg, 1.01 mmol, 1 equiv) in DCM (2.7 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 1 hour, at which point Hunig's base (1.06 mL, 6.09 mmol, 6 equiv) was added. After 30 minutes, the reaction was partitioned between sodium bicarbonate and DCM, and the aqueous phase was extracted with DCM (3×20 mL), the combined organic extracts were washed with water, dried (MgSO4), and concentrated. The resulting yellow residue was purified via flash chromatography on silica gel column (ethyl acetate/hexanes) to yield 2-(3-chloropyrazin-2-ylamino)-1-((3aS,4R,6aR)-2,2-dimethyl-6-(trityloxymethyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)ethanone (1-7) as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.93 (d, 1H, J=3 Hz), 7.64 (d, 1H, J=3 Hz), 7.21-7.49 (m, 15H), 5.94 (s, 1H), 5.62 (m, 1H), 4.97 (t, 1H, J=6 Hz), 4.60-4.77 (2 d, 1H, J=7 Hz), 3.95 (d, 1H, J=14 Hz), 3.75 (m, 2H), 3.31 (m, 1H), 1.36 (s, 3H), 1.33 (s, 3H).

Workup

  1. additionwas added
  2. waitAfter 30 minutes
  3. customthe reaction was partitioned between sodium bicarbonate and DCM
  4. extractionthe aqueous phase was extracted with DCM (3×20 mL)
  5. washthe combined organic extracts were washed with water
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe resulting yellow residue was purified via flash chromatography on silica gel column (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-cbe7b19b166748adab72b532595bb979
Source dataset
uspto-grants-2012_12
Patent number
US08329697B2

Reaction notes

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