Tetrahydrofuran → N-(2-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-pyridine-4-carbonyl}-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

HRID 419151Notes

Reaction equation

HRID 419151 reaction equation
[C:1]([Si:5]([CH3:18])([CH3:17])OCCOC1C=C(I)C=CN=1)([CH3:4])([CH3:3])[CH3:2].[CH:19]([Mg]Cl)([CH3:21])[CH3:20].CON(C)[C:27]([C:29]1[C:34]([N:35]([S:39]([C:42]2[CH:47]=[CH:46][C:45]([Cl:48])=[C:44]([C:49]([F:52])([F:51])[F:50])[CH:43]=2)(=[O:41])=[O:40])[CH2:36][O:37][CH3:38])=[CH:33][C:32]([Cl:53])=[CH:31][N:30]=1)=[O:28].[Cl-].[NH4+:56].[CH2:57]1[CH2:61][O:60][CH2:59][CH2:58]1>C(Cl)Cl>[C:1]([Si:5]([CH3:18])([CH3:17])[O:60][CH2:59][CH2:58][C:57]1[CH:61]=[C:21]([C:27]([C:29]2[C:34]([N:35]([CH2:36][O:37][CH3:38])[S:39]([C:42]3[CH:47]=[CH:46][C:45]([Cl:48])=[C:44]([C:49]([F:52])([F:51])[F:50])[CH:43]=3)(=[O:41])=[O:40])=[CH:33][C:32]([Cl:53])=[CH:31][N:30]=2)=[O:28])[CH:19]=[CH:20][N:56]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 579421195-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid methoxy-methyl-amideHCID 579424932-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-4-iodo-pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 57942209N-(2-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-pyridine-4-carbonyl}-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-4-iodo-pyridine (305 mg, 0.805 mmol) was dissolved in 1 mL of dry THF. To this solution isopropylmagnesium chloride solution (2 M in THF, 0.44 mL, 0.88 mmol) was added at room temperature. After 30 minutes this solution was added to a solution of 5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid methoxy-methyl-amide (283 mg, 0.564 mmol) in 1 mL dry THF at −78° C. The mixture was allowed to warm up to room temperature and stirred overnight followed by addition of 5 mL of aqueous saturated ammonium chloride and extraction with 15 mL DCM. The organic solution was evaporated under reduced pressure and purified on a 4 g silica column eluted with a gradient of 10-40% ethyl acetate in hexanes to yield 205 mg of N-(2-{2-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-pyridine-4-carbonyl}-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide as a colorless oil.

Workup

  1. customThe organic solution was evaporated under reduced pressure
  2. custompurified on a 4 g silica column
  3. washeluted with a gradient of 10-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7e64fb27fb724e79b1ca481d0decdbef
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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