4-Toluenesulfonyl chloride → 6-Bromo-1-tosyl-1H-pyrrolo[3,2-b]pyridine

HRID 75267Notes

Reaction equation

HRID 75267 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[NH:10][CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[S:11](Cl)([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12]>[H-].[Na+].CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 242292566-Bromo-1H-pyrrolo[3,2-b]pyridine

Product 1

HCID 867079586-Bromo-1-tosyl-1H-pyrrolo[3,2-b]pyridine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 24758Sodium hydrideSolvent

Procedure

Scheme B shows a general method for preparing substituted 4-azaindoles (compounds A1 and A3) depicted in Scheme A. The method begins with the installation of an amine protecting group (G) on starting material B1, in which for example, 6-bromo-1H-pyrrolo[3,2-b]pyridine is reacted with TsCl in sodium hydride and DMF to give 6-bromo-1-tosyl-1H-pyrrolo[3,2-b]pyridine. Treatment of the resulting protected intermediate B2 with an oxidizing agent (e.g., mCPBA) gives an N-oxide intermediate B3, which undergoes cyanation via, for example, reaction with trimethylsilyl cyanide in the presence of base (e.g., tertiary amine such as Et3N) and DMF. The resulting intermediate B4 is deprotected (e.g., Ts is removed via contact with aq NaOH) and is optionally N-alkylated through reaction with an alkyl halide B6 (e.g., X2 is I) under basic conditions (e.g., NaH in DMF). As in Scheme A, reaction of the resulting bromide B7 with a boronic acid or boronate, stannane, or amine (A4) under Suzuki, Stille, or Buchwald conditions, respectively, gives an R1-substituted 4-azaindole intermediate B8. Treatment of bromide B7 or intermediate B8 with a reducing agent (e.g., borane-THF) or reaction with an alkyl-Grignard or alkyl-lithium reagent followed by reduction with sodium borohydride gives, respectively, an amine intermediate B9 or desired compound A1. As in Scheme A, reaction of the amine intermediate B9 with a 6-halopyrimidine derivative A2 gives desired compound A3.

Sources & evidence

ORD record
ord-fa32cbdf80bb49c18f31c1ce6024c0b6
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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