Ammonia → 3-{4-Hydroxymethyl-5-[(2'-sulfamoyl-biphenyl-4-ylamino)-methyl]-pyridin-3-yloxymethyl}-benzamidine

HRID 2373308Notes

Reaction equation

HRID 2373308 reaction equation
Cl.C([NH:6][S:7]([C:10]1[C:11]([C:16]2[CH:21]=[CH:20][C:19]([NH:22][CH2:23][C:24]3[CH:25]=[N:26][C:27](C)=[C:28]([O:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([C:40]#[N:41])[CH:35]=4)[C:29]=3[CH2:30][OH:31])=[CH:18][CH:17]=2)=[CH:12][CH:13]=[CH:14][CH:15]=1)(=[O:9])=[O:8])(C)(C)C.[NH3:43].CO>C(O)C>[OH:31][CH2:30][C:29]1[C:24]([CH2:23][NH:22][C:19]2[CH:20]=[CH:21][C:16]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:7](=[O:9])(=[O:8])[NH2:6])=[CH:17][CH:18]=2)=[CH:25][N:26]=[CH:27][C:28]=1[O:32][CH2:33][C:34]1[CH:35]=[C:36]([CH:37]=[CH:38][CH:39]=1)[C:40]([NH2:41])=[NH:43]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 887MethanolHCID 598525264'-{[5-(3-Cyano-benzyloxy)-4-hydroxymethyl-6-methyl-pyridin-3-ylmethyl]-amino}-biphenyl-2-sulfonic acid tert-butylamide

Product 1

HCID 117133113-{4-Hydroxymethyl-5-[(2'-sulfamoyl-biphenyl-4-ylamino)-methyl]-pyridin-3-yloxymethyl}-benzamidineYield 97%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Hydrogen chloride gas was bubbled into a suspension of 4′-{[5-(3-cyano-benzyloxy)-4-hydroxymethyl-6-methyl-pyridin-3-ylmethyl]-amino}-biphenyl-2-sulfonic acid tert-butylamide (13) (100 mg, 0.17 mmol) in absolute ethyl alcohol (30 mL) at 0° C. for 30 minutes. The septum was replaced and the reaction mixture was stirred at room temperature overnight. Hydrogen chloride gas was purged with nitrogen gas for 2 hours and the solvent evaporated to give the crude amide ester as a solid. Ammonia in methyl alcohol (30 mL, 7 M, 350 mmol) was added to the crude amide ester and the reaction mixture was stirred overnight at room temperature. The solvent was evaporated and the product purified on a silica gel column using a mixture of dichloromethane:methyl alcohol (4:1) as eluant to give the corresponding 3-{4-hydroxymethyl-5-[(2′-sulfamoyl-biphenyl-4-ylamino)-methyl]-pyridin-3-yloxymethyl}-benzamidine (14) (90 mg, 97% yield) as a colorless powder.

Workup

  1. customHydrogen chloride gas was purged with nitrogen gas for 2 hours
  2. customthe solvent evaporated
  3. customto give the crude amide ester as a solid
  4. stirringthe reaction mixture was stirred overnight at room temperature
  5. customThe solvent was evaporated
  6. customthe product purified on a silica gel column
  7. additiona mixture of dichloromethane:methyl alcohol (4:1) as eluant

Sources & evidence

ORD record
ord-b198ebe794dd47be903145be40ee65ec
Source dataset
uspto-grants-2008_12
Patent number
US07459468B2

Reaction notes

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