Chloride → HCID 58268098, compound

HRID 1898282Notes

Reaction equation

HRID 1898282 reaction equation
[C:1]([Si:5]([CH3:17])([CH3:16])[N:6]1[C:10]2=[CH:11][CH:12]=[N:13][C:14](I)=[C:9]2[CH:8]=[CH:7]1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:29]([C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[CH:40]=[O:41])[CH2:30][O:31][CH3:32])(=[O:28])=[O:27])=[CH:22][C:21]=1[C:42]([F:45])([F:44])[F:43]>C1COCC1>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:29]([C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[CH:40]([OH:41])[C:10]2[CH:11]=[CH:12][N:13]=[C:14]3[N:6]([Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:17])[CH3:16])[CH:7]=[CH:8][C:9]=23)[CH2:30][O:31][CH3:32])(=[O:27])=[O:28])=[CH:22][C:21]=1[C:42]([F:44])([F:45])[F:43]

Participants

5

Reactant 3

HCID 312ChlorideHCID 58268201HCID 58268201, compoundHCID 86653548HCID 86653548, compound

Product 1

HCID 58268098HCID 58268098, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(tert-butyl-dimethyl-silanyl)-4-iodo-1H-pyrrolo[2,3-d]pyridine (97.4 mg, 0.27 mmol) in THF (2 mL) under nitrogen atmosphere at 0° C. was added drop wise isopropylmagnisum chloride (2 M solution in THF, 0.27 mL, 0.54 mmol). The mixture was then stirred for 30 min at 0° C. followed by the addition of a solution of 4-chloro-N-(5-chloro-2-formyl-phenyl)-N-methoxymethyl-3-trifluoromethyl-benzene sulfonamide (120 mg, 0.27 mmol) in THF (2 mL) at 0° C. The mixture was stirred at room temperature for overnight, quenched with saturated aqueous NH4Cl solution (5 mL) and extracted with EtOAc (2×25 mL). Combined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL), dried (anhydrous Na2SO4) and concentrated under reduced pressure. Obtained residue was column purified (SiO2, 30% EtOAc-hexanes) to obtain 4-chloro-N-{5-chloro-2-[hydroxy-(1-(tert-butyl-dimethyl-silanyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-methyl]-phenyl}-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (88 mg) in 48% yield. ESMS m/z (relative intensity): 674 (M+H)+ (100).

Workup

  1. stirringThe mixture was stirred at room temperature for overnight
  2. customquenched with saturated aqueous NH4Cl solution (5 mL)
  3. extractionextracted with EtOAc (2×25 mL)
  4. washCombined organic layers were washed with saturated aqueous NH4Cl solution (25 mL), brine (25 mL)
  5. dry with materialdried (anhydrous Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. custompurified (SiO2, 30% EtOAc-hexanes)

Sources & evidence

ORD record
ord-b34c37233ab04e13b3a7740b5fb1cc8f
Source dataset
uspto-grants-2013_08
Patent number
US08519135B2

Reaction notes

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