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

HRID 1952154Notes

Reaction equation

HRID 1952154 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 79.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 1-Benzenesulfonyl-5-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine (581, 4.36 g, 10.4 mmol) in tetrahydrofuran (100.0 mL) at −40° C. under nitrogen, isopropylmagnesium chloride (2.0 M in tetrahydrofuran. 5.06 mL) was added slowly. The reaction was allowed to warm to 5° C. over 60 minutes, then cooled to −40° C., followed by adding 2-methylsulfanyl-pyrimidine-5-carbaldehyde (607, 1.30 g, 8.43 mmol, dissolved in tetrahydrofuran 15.0 mL). The reaction was allowed to warm to 10° C. over 2 hours. The reaction was poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 2% to 15% methanol in dichloromethane to give the desired compound (608, 3.00 g, 79.6%). 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 was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by silica gel column chromatography
  8. washeluting with 2% to 15% methanol in dichloromethane

Sources & evidence

ORD record
ord-605f8c9ecde54a11b52894224da13f28
Source dataset
uspto-grants-2013_03
Patent number
US08404700B2

Reaction notes

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