Hydrochloric Acid → HCID 10292239, compound

HRID 1827211Notes

Reaction equation

HRID 1827211 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=O)[N:18](OC)[CH3:19])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[H][H].N[C:40]1[CH:45]=[CH:44]N=[C:42]([NH2:46])[C:41]=1[NH2:47].Cl.[OH-].[Na+]>[Ni].C(O)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][NH:18][C:19]2[C:42]3[N:46]=[CH:23][NH:47][C:41]=3[CH:40]=[CH:45][CH:44]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 22135565Pyridine-2,3,4-triamineHCID 22574154Benzyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 10292239HCID 10292239, compound

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 284Formic AcidSolvent

Procedure

EXAMPLE 105 was prepared from 1H-benzoimidazol-4-ylamine (The 1H-benzoimidazol-4-ylamine was prepared by heating 1.5 g of 3-nitro-benzene-1,2-diamine in 50 mL of triethyl orthoformate with 10 mg of p-toluenesulfonic acid monohydrate at reflux overnight, concentration to dryness under reduced pressure, hydrolysis with refluxing 3N HCl for 1 h and neutralization with NaOH. Then, cooling and collection yielded the 4-nitro-benzimidazole product by filtration. Catalytic reduction using Raney Nickel® in ethanol under 1 atm of hydrogen for 1 h gave 1H-benzoimidazol-4-ylamine as an air sensitive solid) and 4-formyl-piperidine-1-carboxylic acid benzyl ester (prepared from 4-(N-methoxy-N-methyl-carbamoyl)-piperidine-1-carboxylic acid benzyl ester, using the procedures described by S. Nahm and S. W. Weinreb, Tetrahedron Letters, 22:3815–3818(1981)) on a 1 mmol scale by reductive amination in 5 mL of 1,2-dichloromethane using sodium triacetoxyborohydride over 0.5 of Raney Nickel® under 1 atm of hydrogen for 1 h, followed by immediate conversion of the crude, air sensitive triaminopyridine into the imidazo[4,5b]pyridine by heating with 51 mL of 96% formic acid and 2 mL of 37% hydrochloric acid at reflux overnight. The free base was liberated with sodium hydroxide and purified by preparative chromatography, eluting with 90:10 chloroform:methanol: MS (m+1)=365.5.

Workup

  1. customfor 1 h
  2. temperatureat reflux overnight
  3. custompurified by preparative chromatography
  4. washeluting with 90:10 chloroform

Sources & evidence

ORD record
ord-44bc90ea845e4ff2b5c7f2a74a6099fc
Source dataset
uspto-grants-2006_05
Patent number
US07053089B2

Reaction notes

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