Trimethylsilyl iodide → HCID 11563152, compound

HRID 1785996Notes

Reaction equation

HRID 1785996 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C@H:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([C:22]([C:24]3[CH:25]=[N:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=3)=[O:23])[C@@H:14]([CH3:32])[CH2:13]2)[C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.[Si](I)(C)(C)C.[Cl:38][C:39]1[CH:44]=[CH:43][C:42]([N:45]([C@H:49]2[C:58]3[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=3)[N:52]([C:59]([C:61]3[CH:62]=[N:63][C:64]([OH:67])=[CH:65][CH:66]=3)=[O:60])[C@@H:51]([CH3:68])[CH2:50]2)[C:46](=[O:48])[CH3:47])=[CH:41][CH:40]=1.Br[CH2:70][CH2:71][C:72]([CH3:78])([CH3:77])[C:73]([O:75][CH3:76])=[O:74].[Al]>C(Cl)Cl.CN(C)C=O.C(=O)([O-])[O-].[Ag+2]>[C:9]([N:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[C@H:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([C:22]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:71][C:72]([CH3:78])([CH3:77])[C:73]([O:75][CH3:76])=[O:74])=[N:26][CH:25]=2)=[O:23])[C@@H:14]([CH3:32])[CH2:13]1)(=[O:11])[CH3:10].[C:46]([N:45]([C:42]1[CH:43]=[CH:44][C:39]([Cl:38])=[CH:40][CH:41]=1)[C@H:49]1[C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[N:52]([C:59]([C:61]2[CH:66]=[CH:65][C:64](=[O:67])[N:63]([CH2:70][CH2:71][C:72]([CH3:78])([CH3:77])[C:73]([O:75][CH3:76])=[O:74])[CH:62]=2)=[O:60])[C@@H:51]([CH3:68])[CH2:50]1)(=[O:48])[CH3:47]

Participants

10

Reactant 5

HCID 85247Trimethylsilyl iodideHCID 5359268AluminumHCID 14928877Butanoic acid, 4-bromo-2,2-dimethyl-, methyl ester2×HCID 68924340HCID 68924340, compound2×HCID 178474182HCID 178474182, compound

Product 2

HCID 11563152HCID 11563152, compoundYield 32%HCID 57595494HCID 57595494, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 178418647HCID 178418647, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 4-[(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}pyridin-2-yl)oxy]-2,2-dimethylbutanoate was prepared from (2S,4R)-N-(4-chloro-phenyl)-N-[1-(6-methoxy-pyridine-3-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide by deprotection of the methoxy and elaboration. (2S,4R)-N-(4-chloro-phenyl)-N-[1-(6-methoxy-pyridine-3-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.062 g, 0.13 mmol) was dissolved in methylene chloride and TMSI (0.020 mL, 0.13 mmol) was added and stirred at room temperature for 14 h. The reaction mixture was concentrated down and methanol was added and stirring was continued for 10 h, concentrated down and used directly. N-(4-chlorophenyl)-N-{(2S,4R)-1-[(6-hydroxypyridin-3-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide (0.060 g, 0.13 mmol) was dissolved in 2 mL of dimethylformamide, followed by 0.046 g of methyl 4-bromo-2,2-dimethylbutanoate (0.20 mmol) and 0.057 g of silver carbonate (0.20 mmol). The flask was covered with aluminum foil and the lights were turned off in the enclosure. The reaction was allowed to heat to 80° C. for 24 h. Additional methyl 4-bromo-2,2-dimethylbutanoate (0.046 g, 0.20 mmol) was added and continued stirring at 80° C. for 24 h. The reaction was concentrated down and partitioned between ethyl acetate and water. The organics were collected together and dried over MgSO4, filtered and concentrated. The residue was purified with 2% methanol/98% methylene chloride to 5% methanol/95% methylene chloride to 10% methanol/90% methylene chloride. Two products were obtained the O- and N-alkylated product, methyl 4-[(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}pyridin-2-yl)oxy]-2,2-dimethylbutanoate (0.025 g, 32%) and methyl 4-[5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}-2-oxopyridin-1(2H)-yl]-2,2-dimethylbutanoate (0.025 g, 32%).

Workup

  1. concentrationThe reaction mixture was concentrated down and methanol
  2. additionwas added
  3. stirringstirring
  4. waitwas continued for 10 h
  5. concentrationconcentrated down
  6. temperatureto heat to 80° C. for 24 h
  7. stirringcontinued stirring at 80° C. for 24 h
  8. concentrationThe reaction was concentrated down
  9. custompartitioned between ethyl acetate and water
  10. customThe organics were collected together
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified with 2% methanol/98% methylene chloride to 5% methanol/95% methylene chloride to 10% methanol/90% methylene chloride

Sources & evidence

ORD record
ord-8ebfd296bffc4168bc484359eb1ddf50
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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