4-Toluenesulfonyl chloride → benzyl 4-[(2,4,4-trimethylpentan-2-yl)amino]-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

HRID 2201794Notes

Reaction equation

HRID 2201794 reaction equation
[N:1]1([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[C:9]2[CH:8]=[CH:7][N+:6]([O-])=[CH:5][C:4]=2[CH:3]=[CH:2]1.[CH3:21][C:22]([NH2:29])([CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:23].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.ClCCl>[CH3:21][C:22]([NH:29][C:5]1[C:4]2[CH:3]=[CH:2][N:1]([C:11]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:12])[C:9]=2[CH:8]=[CH:7][N:6]=1)([CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:23]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 61017tert-OctylamineHCID 71061742benzyl 1H-pyrrolo[3,2-c]pyridine-1-carboxylate 5-oxide

Product 1

HCID 71061424benzyl 4-[(2,4,4-trimethylpentan-2-yl)amino]-1H-pyrrolo[3,2-c]pyridine-1-carboxylateYield 54.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of benzyl 1H-pyrrolo[3,2-c]pyridine-1-carboxylate 5-oxide (500 mg, 1.9 mmol, Step b) in chloroform was treated dropwise with 2,4,4-trimethylpentan-2-amine (1.57 mL, 8.5 mmol) and stirred for about 15 minutes. The mixture was cooled to 0° C. followed by the portion wise addition of p-toluenesulphonyl chloride (745 mg, 4.2 mmol). The reaction mixture was then stirred at room temperature for 1 hour, diluted with dichloromethane and washed with saturated sodium bicarbonate solution. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under vacuum to yield viscous oil. The crude product was purified by silica gel (100-200 mesh) column chromatography using ethyl acetate in hexane (1.5%) as eluent to yield benzyl 4-[(2,4,4-trimethylpentan-2-yl)amino]-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (390 mg, 43%) as a pale yellow solid.

Workup

  1. stirringThe reaction mixture was then stirred at room temperature for 1 hour
  2. washwashed with saturated sodium bicarbonate solution
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customto yield viscous oil
  7. customThe crude product was purified by silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-380d834d1df24685b2e8d3072c4cba4d
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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