Ammonium Chloride → (1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-(2-methylsulfanyl-pyrimidin-5-yl)-methanol

HRID 1396144Notes

Reaction equation

HRID 1396144 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12](I)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Cl)(C)C.[CH3:26][S:27][C:28]1[N:33]=[CH:32][C:31]([CH:34]=[O:35])=[CH:30][N:29]=1.[Cl-].[NH4+]>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12]([CH:34]([C:31]3[CH:30]=[N:29][C:28]([S:27][CH3:26])=[N:33][CH:32]=3)[OH:35])=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 31518652-(Methylthio)-5-pyrimidinecarbaldehydeHCID 242292391-Benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 57619161(1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-(2-methylsulfanyl-pyrimidin-5-yl)-methanolYield 55.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 1-benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine (28, 8.40 g, 20.1 mmol) in 96.3 mL of tetrahydrofuran at −40° C. under nitrogen, isopropylmagnesium chloride (10.1 mL, 2.0 M in tetrahydrofuran, 20.3 mmol) is added slowly. The reaction is allowed to warm to 5° C. over 60 minutes, then cooled to −40° C., followed by addition of 2-methylsulfanyl-pyrimidine-5-carbaldehyde (34, 2.50 g, 16.2 mmol) in 15.0 mL of tetrahydrofuran. The reaction is allowed to warm to 10° C. over 2 hours, then poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with 40-100% ethyl acetate in hexane. Appropriate fractions are combined and the solvents removed under vacuum to provide the desired compound as an off-white solid (35, 4.0 g). MS (ESI) [M+H+]+=447.2.

Workup

  1. temperaturecooled to −40° C.
  2. temperatureto warm to 10° C. over 2 hours
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated under vacuum
  7. customThe resulting material is purified by silica gel column chromatography
  8. washeluting with 40-100% ethyl acetate in hexane
  9. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-e8ab6196839d49dc9e8c15886ca5b664
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

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