Dimethyl Sulfide → HCID 178502471, compound

HRID 1751397Notes

Reaction equation

HRID 1751397 reaction equation
CSC.ClN1C(=O)CCC1=O.[OH:12][C@@H:13]1[CH2:17][N:16]([C:18](=[O:28])[C@@H:19]([NH:23][C:24]([O:26][CH3:27])=[O:25])[CH:20]([CH3:22])[CH3:21])[C@H:15]([C:29]2[NH:30][CH:31]=[C:32]([C:34]3[CH:39]=[CH:38][C:37]([C:40]4[CH:41]=[C:42]5[C:47](=[CH:48][CH:49]=4)[CH:46]=[C:45]([C:50]4[NH:54][C:53]([C@@H:55]6[CH2:59][CH2:58][CH2:57][N:56]6[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])=[N:52][CH:51]=4)[CH:44]=[CH:43]5)=[CH:36][CH:35]=3)[N:33]=2)[CH2:14]1.C(N(CC)CC)C>ClCCl>[CH3:27][O:26][C:24]([NH:23][C@@H:19]([CH:20]([CH3:22])[CH3:21])[C:18]([N:16]1[CH2:17][C:13](=[O:12])[CH2:14][C@H:15]1[C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][C:37]([C:40]3[CH:41]=[C:42]4[C:47](=[CH:48][CH:49]=3)[CH:46]=[C:45]([C:50]3[NH:54][C:53]([C@@H:55]5[CH2:59][CH2:58][CH2:57][N:56]5[C:60]([O:62][C:63]([CH3:65])([CH3:64])[CH3:66])=[O:61])=[N:52][CH:51]=3)[CH:44]=[CH:43]4)=[CH:36][CH:35]=2)[N:33]=1)=[O:28])=[O:25]

Participants

6

Reactant 4

HCID 1068Dimethyl SulfideHCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 178502466HCID 178502466, compound

Product 1

HCID 178502471HCID 178502471, compoundYield 90.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Dimethyl sulfide (164 μL, 2.23 mmol) was added dropwise to a solution of N-chlorosuccinimide (238 mg, 2.12 mmol) in dichloromethane (10 mL) at 0° C. After 15 minutes the mixture was cooled to −15° C. (ice-salt bath). A solution of (S)-tert-butyl 2-(5-(6-(4-(2-((2S,4S)-4-hydroxy-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (809 mg, 1.06 mmol) in dichloromethane (5 mL) was added dropwise. The temperature was not allowed to go above −10° C. After 2 hours a solution of triethylamine (316 μL, 2.23 mmol) in dichloromethane (2 mL) was added dropwise and the mixture was allowed to warm to room temperature at which point the reaction was complete. The mixture was washed with saturated ammonium chloride (3×10 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product containing fractions were combined and the solvent was removed under reduced pressure to yield (S)-tert-butyl 2-(5-(6-(4-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-oxopyrrolidin-2-yl)-1H-imidazol-4-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (734 mg, 0.96 mmol, 90%).

Workup

  1. customto go above −10° C
  2. washThe mixture was washed with saturated ammonium chloride (3×10 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. additionThe product containing fractions
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-106f5e20c5af468c949795b07168d2ab
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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