4-Toluenesulfonyl chloride → HCID 57447072, compound

HRID 2366695Notes

Reaction equation

HRID 2366695 reaction equation
C1C=C(Cl)C=C(C(OO)=O)C=1.[N:12]1([C:18](=[O:38])[CH2:19][CH2:20][CH2:21][N:22]2[C:34]3[C:33]4[N:32]=[CH:31][CH:30]=[CH:29][C:28]=4[N:27]=[CH:26][C:25]=3[N:24]=[C:23]2[CH2:35][CH2:36][CH3:37])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[OH-].[NH4+:40].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[N:12]1([C:18](=[O:38])[CH2:19][CH2:20][CH2:21][N:22]2[C:34]3[C:33]4[N:32]=[CH:31][CH:30]=[CH:29][C:28]=4[N:27]=[C:26]([NH2:40])[C:25]=3[N:24]=[C:23]2[CH2:35][CH2:36][CH3:37])[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 57447073HCID 57447073, compound

Product 1

HCID 57447072HCID 57447072, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

mCPBA (1.18 g, 6.86 mmol) was added to a solution of 1-(4-morpholin-4-yl-4-oxobutyl)-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridine (1.80 g, 4.90 mmol) in chloroform (25 mL); the reaction was stirred for two hours at ambient temperature. Ammonium hydroxide (10 mL) was added followed by p-toluenesulfonyl chloride (1.03 g, 5.39 mmol). The reaction was stirred for one hour and partitioned between saturated aqueous sodium bicarbonate (75 mL) and dichloromethane (70 mL). The aqueous layer was extracted with dichloromethane (2×25 mL), and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting brown solid was triturated twice with acetonitrile and then purified by column chromatography using a HORIZON HPFC system (an automated, modular high-performance flash purification product available from Biotage, Inc.; Charlottesville, Va., USA) using a FLASH 40+M cartridge (also available from Biotage, Inc.). The polar component of the eluent was chloroform:methanol:ammonium hydroxide 80:18:2 (CMA). The purification was carried out eluting with chloroform:CMA in a gradient from 100:0 to 75:25. The resulting solid was dried under high vacuum at 80° C. to provide 0.583 g of 1-(4-morpholin-4-yl-4-oxobutyl)-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine as an off-white powder, mp 196-197° C.

Workup

  1. stirringThe reaction was stirred for one hour
  2. custompartitioned between saturated aqueous sodium bicarbonate (75 mL) and dichloromethane (70 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (2×25 mL)
  4. dry with materialthe combined organic fractions were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting brown solid was triturated twice with acetonitrile
  8. custompurified by column chromatography
  9. custommodular high-performance flash purification product available from Biotage, Inc
  10. customThe purification
  11. washwas carried out eluting with chloroform
  12. customThe resulting solid was dried under high vacuum at 80° C.

Sources & evidence

ORD record
ord-2117bc3914c946fbae2c795ee79b9d15
Source dataset
uspto-grants-2014_04
Patent number
US08697873B2

Reaction notes

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