Trifluoroacetic acid → 2-({[(8-hydroxy-1,6-naphthyridin-7-yl)carbonyl]amino}methyl)-1H-benzimidazol-1-ium Trifluoroacetate

HRID 896282Notes

Reaction equation

HRID 896282 reaction equation
ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.C(O[C:17]([C:19]1[C:24]([CH2:25][N:26]([CH2:37][C:38]([O:40]C)=O)S(C2C=CC(C)=CC=2)(=O)=O)=[CH:23][CH:22]=[CH:21][N:20]=1)=[O:18])(C)C.C(N(C(C)C)CC)(C)C.O.[Cl-].[Cl-].[NH3+:54][CH2:55][C:56]1[NH2+:60][C:59]2[CH:61]=[CH:62][CH:63]=[CH:64][C:58]=2[N:57]=1.[C:65]([OH:71])([C:67]([F:70])([F:69])[F:68])=[O:66]>CN(C=O)C>[F:68][C:67]([F:70])([F:69])[C:65]([O-:71])=[O:66].[OH:18][C:17]1[C:37]([C:38]([NH:54][CH2:55][C:56]2[NH2+:60][C:59]3[CH:61]=[CH:62][CH:63]=[CH:64][C:58]=3[N:57]=2)=[O:40])=[N:26][CH:25]=[C:24]2[C:19]=1[N:20]=[CH:21][CH:22]=[CH:23]2

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 43835646Benzimidazol-2-ylmethylamine, oxamethane, chloride, chlorideHCID 599831603-{[Methoxycarbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}-pyridine-2-carboxylic Acid Isopropyl Ester

Product 1

HCID 223500442-({[(8-hydroxy-1,6-naphthyridin-7-yl)carbonyl]amino}methyl)-1H-benzimidazol-1-ium Trifluoroacetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Triphosgene (0.556 g, 1.87 mmol) was added over 20 mins to a solution of the acid from Step 1. (0.89 g, 4.68 mmol) and diisopropylethylamine 3.26 ml, 18.7 mmol) in DMF (22 ml) at 0° C. The dark solution was allowed to warm to room temperature and stirred a further 1 hr. 2-(ammoniomethyl)-1H-benzimidazol-1-ium dichloride hydrate (25.0 mg, 1.05 mmol) was treated with a portion of the above solution (0.58 ml, 0.07 mmol) and the resulting mixture was stirred at room temperature for 16 hrs. The solution was treated with TFA (0.025 ml) and purified by preparative HPLC. (Gilson semi preparative HPLC system and a YMC Combiprep Pro Column (50×20 mm I.D., C18, S-5 um, 120A) (available from Waters) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 ml/min) to afford the trifluoroacetate salt of the title compound after lyophilization.

Workup

  1. customat 0° C
  2. stirringthe resulting mixture was stirred at room temperature for 16 hrs
  3. custompurified by preparative HPLC
  4. wash(Gilson semi preparative HPLC system and a YMC Combiprep Pro Column (50×20 mm I.D., C18, S-5 um, 120A) (available from Waters) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 ml/min)

Sources & evidence

ORD record
ord-22dd52fbf50647fabf4cdd7503f820b4
Source dataset
uspto-grants-2005_07
Patent number
US06919351B2

Reaction notes

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