Dimethyl Sulfoxide → HCID 57546061, compound

HRID 913954Notes

Reaction equation

HRID 913954 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[Cl:11][C:12]1[CH:20]=[C:19]([CH:21]([O:24][CH2:25][C:26]2([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)[CH2:22][OH:23])[C:18]2[C:14](=[CH:15][N:16]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[N:17]=2)[CH:13]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:11][C:12]1[CH:20]=[C:19]([CH:21]([O:24][CH2:25][C:26]2([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)[CH:22]=[O:23])[C:18]2[C:14](=[CH:15][N:16]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[N:17]=2)[CH:13]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 57545941HCID 57545941, compound

Product 1

HCID 57546061HCID 57546061, compoundYield 71.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To solution of Methyl Sulfoxide (0.197 ml, 2.77 mmol) in DCM (12 ml) at −78° C. was added oxalyl chloride (0.694 ml, 1.387 mmol) dropwise. The solution was stirred at −78° C. for 0.5 h. A solution of Tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-hydroxyethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (400 mg, 0.631 mmol) in DCM (12 ml) was then added dropwise. The slurry was stirred at −78° C. for 2 h before addition of N,N-Diisopropylethylamine (0.549 ml, 3.15 mmol) dropwise. The solution was slowly warmed up and stirred at room temperature for 3 h. It was then washed with iced 1M HCl and brine, dried over MgSO4, filtered and concentrated. The residual light yellow oil was purified by Biotage LC (35% EtOAc/Hexane) to afford title compound (286.3 mg, 0.453 mmol, 71.8% yield) as yellow foam solid. 1H-NMR (CDCl3, 500 MHz) δ 9.61 (s, 1H), 8.05, s, 1H), 7.60 (d, J=1.8 Hz, 1H), 7.33 (m, 2H), 7.04 (m, 2H), 7.02 (buried, 1H), 5.67 (m, 2H), 3.60 (app t, J=8.3 Hz, 2H), 3.45-3.85 (m, 3H), 3.45 (d, J=9.1 Hz, 1H), 2.18 (m, 2H), 1.95 (m, 2H), 1.75 (m, 1H), 1.43 (s, 9H), 0.91 (app t, J=8.2 Hz, 2H), −0.04 (s, 9H). LC/MS (HPLC method 3): tR=4.11 min, 632.3(MH)+.

Workup

  1. temperatureThe solution was slowly warmed up and
  2. stirringstirred at room temperature for 3 h
  3. washIt was then washed with iced 1M HCl and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residual light yellow oil was purified by Biotage LC (35% EtOAc/Hexane)

Sources & evidence

ORD record
ord-dfc84a55edaa4ec389b37d23b03fb80b
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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