Hydrochloric Acid → HCID 68530704, compound

HRID 644234Notes

Reaction equation

HRID 644234 reaction equation
N[CH2:2][CH2:3][O:4][C:5]1[CH:30]=[C:29]([S:31][CH3:32])[CH:28]=[CH:27][C:6]=1[C:7]([NH:9][C:10]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:11]=1[C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][N:16]=1)=[O:13])=[O:8].C=O.[C:35]([BH3-])#[N:36].[Na+].Cl.[C:40](=O)([O-])[O-].[Na+].[Na+]>CO.C(Cl)Cl.C(O)(=O)C.CO>[ClH:21].[Cl:26][C:23]1[CH:24]=[CH:25][C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:27]=[CH:28][C:29]([S:31][CH3:32])=[CH:30][C:5]=2[O:4][CH2:3][CH2:2][N:36]([CH3:35])[CH3:40])=[C:11]([CH:22]=1)[C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][N:16]=1)=[O:13]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 10340Sodium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 57860812HCID 57860812, compound

Product 1

HCID 68530704HCID 68530704, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a mixture of 2-[2-(2-aminoethoxy)-4-(methylthio)benzoylamino]-5-chloro-N-(5-chloropyridin-2-yl)benzamide (1.25 g, 2.47 mmol), paraformaldehyde (312 mg, 10.4 mmol) and methanol (30 mL) was added acetic acid to obtain a pH of 4.0. Sodium cyanoborohydride (311 mg, 4.95 mmol) was added to this mixture. After stirring overnight, the reaction was concentrated, dissolved in 10% MeOH/CHCl3, and passed through an SCX column. The eluent was concentrated and chromatographed on silica gel (1:10 EtOAc:CH2Cl2 to 1:10 MeOH:CH2Cl2) to give impure product. The impure product was dissolved in 5% MeOH/CH2Cl2 and 1 N HCl and stirred for one hour. The mixture was basified with 50% satd sodium carbonate and extracted with CH2Cl2. The organic layer was concentrated and purified by HPLC on a Vydac C18 column [preparative: gradient 20% CH3 CN/(0.01% HCl in H2O) to 80% CH3 CN/(0.01% HCl in H2O) over 6 h on a 5×25 cm column; analytical: 5% CH3 CN/(0.1% TFA in H2O) to 70% CH3 CN/(0.1% TFA in H2O) on a 0.46×25 cm column] to give the title product as a white solid (329 mg, 62%).

Workup

  1. customto obtain a pH of 4.0
  2. concentrationthe reaction was concentrated
  3. dissolutiondissolved in 10% MeOH/CHCl3
  4. concentrationThe eluent was concentrated
  5. customchromatographed on silica gel (1:10 EtOAc:CH2Cl2 to 1:10 MeOH:CH2Cl2)
  6. customto give impure product
  7. extractionextracted with CH2Cl2
  8. concentrationThe organic layer was concentrated
  9. custompurified by HPLC on a Vydac C18 column [preparative: gradient 20% CH3 CN/(0.01% HCl in H2O) to 80% CH3 CN/(0.01% HCl in H2O) over 6 h on a 5×25 cm column

Sources & evidence

ORD record
ord-5b83cd39625e458891216fba7335f68c
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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