Ammonia → HCID 178508172, compound

HRID 1187388

Reaction equation

HRID 1187388 reaction equation
[C:1]1(S(Cl)(=O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(Cl)(=O)=O.[NH3:16].[OH-].[NH4+:18].[C:19](=O)([O-])[O-].[NH4+:23].[NH4+:24].[C:25](=O)(O)[O-].[NH4+:29].P([O-])([O-])([O-])=O.[NH4+].[NH4+].[NH4+].[C:38]1([CH3:48])[CH:43]=[CH:42][C:41](S(Cl)(=O)=O)=[CH:40][CH:39]=1>C(Cl)(Cl)Cl.ClCCl>[NH:16]1[C:2]2[C:3]3[N:24]=[CH:1][CH:6]=[CH:5][C:4]=3[N:23]=[C:39]([NH2:29])[C:38]=2[N:18]=[CH:25]1.[NH:16]1[C:48]2[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[N:23]=[C:2]([NH2:24])[C:1]=2[N:18]=[CH:19]1

Participants

12

Reactant 8

HCID 222AmmoniaHCID 7369Benzenesulfonyl chlorideHCID 73974-Toluenesulfonyl chlorideHCID 14013Ammonium BicarbonateHCID 14923Ammonium Hydroxide2×HCID 31297Methanesulfonyl chlorideHCID 159282Ammonium phosphate, tribasicHCID 517111Ammonium Carbonate

Product 2

HCID 178508172HCID 178508172, compoundHCID 178508191HCID 178508191, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

In step (10) of Reaction Scheme I, a 1H-imidazo[4,5-c][1,5]naphthyridine-5N-oxide, or 1H-imidazo[4,5-c]quinoline-5N-oxide of Formula XXIX is aminated to provide a 1H-imidazo[4,5-c][1,5]naphthyridinamine or 1H-imidazo[4,5-c]quinolin-4-amine of Formula XXX. Step (10) involves the activation of an N-oxide of Formula XXIX by conversion to an ester and then reacting the ester with an aminating agent. Suitable activating agents include alkyl- or arylsulfonyl chlorides such as benzenesulfonyl chloride, methanesulfonyl chloride, orp-toluenesulfonyl chloride. Suitable aminating agents include ammonia, in the form of ammonium hydroxide, for example, and ammonium salts such as ammonium carbonate, ammonium bicarbonate, and ammonium phosphate. The reaction is conveniently carried out by adding ammonium hydroxide to a solution of the N-oxide of Formula XXX in a suitable solvent such as dichloromethane or chloroform and then adding p-toluenesulfonyl chloride. The reaction can be carried out at ambient temperature. Under these reaction conditions, the N-phthalimide protecting group is removed to provide the 1H-imidazo[4,5-c][1,5]naphthyridin4-amine or 1H-imidazo[4,5-c]quinolin-4-amine of Formula XXX or a pharmaceutically acceptable salt thereof, which can be isolated from the reaction mixture using conventional methods.

Workup

  1. customThe reaction
  2. customcan be carried out at ambient temperature
  3. customUnder these reaction conditions
  4. customthe N-phthalimide protecting group is removed

Sources & evidence

ORD record
ord-7f68d3770fb041af9f58adfa07c9a57f
Source dataset
uspto-grants-2014_03
Patent number
US08673932B2

Linked notes

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