tert-butyl N-(3-formylpyridin-2-yl)carbamate → [3-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzene sulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-pyridin-2-yl]-carbamic acid tert-butyl ester

HRID 419166Notes

Reaction equation

HRID 419166 reaction equation
Br[C:2]1[C:7]([N:8]([CH2:23][O:24][CH3:25])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[C:32]([O:36][C:37](=[O:47])[NH:38][C:39]1[C:44]([CH:45]=[O:46])=[CH:43][CH:42]=[CH:41][N:40]=1)([CH3:35])([CH3:34])[CH3:33]>C1COCC1>[C:32]([O:36][C:37](=[O:47])[NH:38][C:39]1[C:44]([CH:45]([C:2]2[C:7]([N:8]([S:9]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=3)(=[O:11])=[O:10])[CH2:23][O:24][CH3:25])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=2)[OH:46])=[CH:43][CH:42]=[CH:41][N:40]=1)([CH3:35])([CH3:33])[CH3:34]

Participants

5

Reactant 3

HCID 14177125tert-butyl N-(3-formylpyridin-2-yl)carbamateHCID 57942086N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamideHCID 178418918HCID 178418918, compound

Product 1

HCID 57942296[3-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzene sulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-pyridin-2-yl]-carbamic acid tert-butyl esterYield 44.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (3.27 g, 6.64 mmol) in THF (20 mL) under nitrogen atmosphere at 0° C. was added dropwise isopropylmagnesium chloride (2 M solution in THF, 6.62 mL, 13.25 mmol). The mixture was then stirred for 30 min at 0° C. followed by the addition of a solution of (3-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (590 mg, 2.65 mmol) in THF (3 mL) at 0° C. The mixture was stirred at room temperature for 3 hours, quenched with saturated aqueous NH4Cl solution (10 mL) and extracted with EtOAc (2×50 mL). Combined organic layers were washed with saturated aqueous NH4Cl solution (50 mL), brine (50 mL), dried (anhydrous Na2SO4) and concentrated under reduced pressure. Obtained residue was column purified (SiO2, 50% EtOAc-hexanes) to obtain [3-({5-chloro-3-[(4-chloro-3-trifluoromethyl-benzene sulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-pyridin-2-yl]-carbamic acid tert-butyl ester (750 mg) in 44% yield as yellow solid. ESMS m/z (relative intensity): 637 (M+H)+ (100).

Workup

  1. stirringThe mixture was stirred at room temperature for 3 hours
  2. customquenched with saturated aqueous NH4Cl solution (10 mL)
  3. extractionextracted with EtOAc (2×50 mL)
  4. washCombined organic layers were washed with saturated aqueous NH4Cl solution (50 mL), brine (50 mL)
  5. dry with materialdried (anhydrous Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. custompurified (SiO2, 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-f42855cb406241ea97b0fdb292f181e0
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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