(4S)-(4-methyl-2,5-dioxoimidazolidin-4-yl)methanesulphonyl chloride → (5S)-5-Methyl-5-[({4-[4-(2,2,3,3,3-pentafluoropropoxy)phenoxy]-piperidin-1-yl}sulphonyl)methyl]imidazolidine-2,4-dione

HRID 1091990Notes

Reaction equation

HRID 1091990 reaction equation
[CH3:1][C@@:2]1([CH2:9][S:10](Cl)(=[O:12])=[O:11])[C:6](=[O:7])[NH:5][C:4](=[O:8])[NH:3]1.Cl.[F:15][C:16]([F:36])([C:32]([F:35])([F:34])[F:33])[CH2:17][O:18][C:19]1[CH:31]=[CH:30][C:22]([O:23][CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[CH:21][CH:20]=1>ClCCl.C(N(CC)CC)C>[CH3:1][C@:2]1([CH2:9][S:10]([N:27]2[CH2:28][CH2:29][CH:24]([O:23][C:22]3[CH:21]=[CH:20][C:19]([O:18][CH2:17][C:16]([F:15])([F:36])[C:32]([F:34])([F:35])[F:33])=[CH:31][CH:30]=3)[CH2:25][CH2:26]2)(=[O:12])=[O:11])[NH:3][C:4](=[O:8])[NH:5][C:6]1=[O:7]

Participants

5

Reactant 2

HCID 16738713(4S)-(4-methyl-2,5-dioxoimidazolidin-4-yl)methanesulphonyl chlorideHCID 86624656HCID 86624656, compound

Product 1

HCID 11519157(5S)-5-Methyl-5-[({4-[4-(2,2,3,3,3-pentafluoropropoxy)phenoxy]-piperidin-1-yl}sulphonyl)methyl]imidazolidine-2,4-dioneYield 17.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

[(4S)-4-methyl-2,5-dioxoimidazolidin-4-yl]methanesulphonyl chloride (0.188 g) was added to a solution of 4-{4-(2,2,3,3,3-pentafluoropropoxy)phenoxy]-piperidine hydrochloride (0.30 g) in dichloromethane (10 ml) and triethylamine (0.70 ml) at ambient temperature. Stirred for 16 hours and evaporated to dryness. The residue was purified by prep HPLC (using λ230 nm as the detecting wavelength) eluting with 0-95% acetonitrile, H2O, +0.2% trifluoroacetic acid. Yielded a solid product, which was dried under vacuum at 50° C. to give the title compound (0.076 g). NMR: (DMSOd6) δ 10.7 (s, 1H), 8.0 (s, 1H), 7.0 (m, 4H), 4.75 (t, 2H), 4.45 (m, 1H), 3.5 (d, 1H), 3.3 (m, 3H), 3.1 (m, 2H), 1.95 (m, 2H), 1.7 (m, 2H), 1.35 (s, 3H). Mass Spectrum: M−H− 513.

Workup

  1. customevaporated to dryness
  2. customThe residue was purified by prep HPLC (
  3. washeluting with 0-95% acetonitrile, H2O, +0.2% trifluoroacetic acid
  4. customYielded a solid product, which
  5. customwas dried under vacuum at 50° C.

Sources & evidence

ORD record
ord-b2f94d880dfc474a949b7e1821789139
Source dataset
uspto-grants-2012_03
Patent number
US08129412B2

Reaction notes

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