Hydrochloric Acid → HCID 66668997, compound

HRID 1617987Notes

Reaction equation

HRID 1617987 reaction equation
Cl.[CH3:2][C:3]1[CH:8]=[C:7]([C:9](=[O:38])[CH2:10][C@H:11]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH:26]=3)=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[CH:6]=[CH:5][N:4]=1.C(N(CC)C(C)C)(C)C.[CH3:48][S:49](Cl)(=[O:51])=[O:50].[O:53]1[CH2:58][CH2:57]OCC1>>[CH3:2][C:3]1[CH:8]=[C:7]([C:9](=[O:38])[CH2:10][C@H:11]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH2:26][CH2:27][NH:28][C:58](=[O:53])[CH:57]=3)=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[CH:6]=[CH:5][N:4]=1.[CH3:48][S:49]([N:28]1[CH2:27][CH:26]=[C:25]([C:22]2[CH:23]=[CH:24][C:19]([C@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])[CH2:10][C:9]([C:7]3[CH:6]=[CH:5][N:4]=[C:3]([CH3:2])[CH:8]=3)=[O:38])=[CH:20][CH:21]=2)[CH2:30][CH2:29]1)(=[O:51])=[O:50]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 66668618HCID 66668618, compound

Product 2

HCID 66668627HCID 66668627, compoundYield 16%HCID 66668997HCID 66668997, compoundYield 35%

Procedure

Hydrogen chloride solution (4 M in 1,4-dioxane, 1.5 mL, 6.0 mmol) was added at room temperature to a solution of (R)-tert-butyl 4-(4-(3-(2-methylpyridin-4-yl)-3-oxo-1-o-tolyl-propyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (example 372, step 1; 200 mg, 403 μmol) in 1,4-dioxane (4 mL), then after 2 h the reaction mixture was evaporated. The residue was suspended in dichloromethane (8 mL), then treated with N,N-diisopropylethylamine (312 mg, 2.42 mmol) and methanesulfonyl chloride (92 mg, 805 μmol) at 0° C. The ice bath was removed, then after 16 h the reaction mixture was partitioned between sat. aq. ammonium chloride solution and dichloromethane. The organic layer was dried over sodium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient, then dichloromethane-methanol 9:1) gave the title compound (27 mg, 16%; light brown foam, MS (ESI+): m/z=411.2 ([M+H]+)) and (R)-3-[4-(1-methane sulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-phenyl]-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one (66 mg, 35%).

Workup

  1. customafter 2 h the reaction mixture was evaporated
  2. customThe ice bath was removed
  3. customafter 16 h the reaction mixture was partitioned between sat. aq. ammonium chloride solution and dichloromethane
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-316ec6ba0c134d6990a46e911aa2c1a8
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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