Hydrochloric Acid → HCID 22010748, compound

HRID 323175Notes

Reaction equation

HRID 323175 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:14]([NH:16][C:17]3[CH:50]=[CH:49][C:20]([C:21]([N:23]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][C:26]=4[O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][C:38]([N:40]4[CH2:45][CH2:44][CH:43]([N:46]([CH3:48])[CH3:47])[CH2:42][CH2:41]4)=[O:39])[CH3:24])=[O:22])=[CH:19][C:18]=3[O:51][CH3:52])=[O:15])=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.[CH2:53]=O.[C:55]([BH3-])#[N:56].[Na+].[ClH:59]>CO.C(O)(=O)C.C(O)C>[ClH:59].[ClH:59].[CH3:53][N:56]([CH3:55])[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:14]([NH:16][C:17]3[CH:50]=[CH:49][C:20]([C:21]([N:23]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][C:26]=4[O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][C:38]([N:40]4[CH2:45][CH2:44][CH:43]([N:46]([CH3:48])[CH3:47])[CH2:42][CH2:41]4)=[O:39])[CH3:24])=[O:22])=[CH:19][C:18]=3[O:51][CH3:52])=[O:15])=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 22010797HCID 22010797, compound

Product 1

HCID 22010748HCID 22010748, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

To a solution of 4-(4′-aminobiphenyl-2-carboxamido)-3-methoxy-N-[2-[5-(4-dimethylaminopiperidin-1-ylcarbonyl)pent-1-yloxy]-4-methylphenyl]-N-methylbenzamide (180 mg) and 37% formalin (3 ml) in methanol (20 ml) and acetic acid (0.5 ml) was added sodium cyanoborohydride (80 mg) at ambient temperature. The mixture was stirred at same temperature for 3 hours and quenched with saturated sodium hydrogen carbonate. The mixture was extracted with ethyl acetate and washed with saturated sodium hydrogen carbonate, brine and dried over sodium sulfate. The solvent was removed by evaporation and the crude product was purified by preparative thin layer chromatography (10% methanol in chloroform) to give free product. To a solution of this product (120 mg) in ethanol (10 ml) was added 1N hydrochloric acid (0.33 ml) and stirred at ambient temperature for 10 minutes. The solvent was removed to give 4-(4′-dimethylaminobiphenyl-2-carboxamido)-3-methoxy-N-[2-[5-(4-dimethylaminopiperidin-1-ylcarbonyl)pent-1-yloxy]-4-methylphenyl]-N-methylbenzamide dihydrochloride (130 mg) as amorphous.

Workup

  1. customquenched with saturated sodium hydrogen carbonate
  2. extractionThe mixture was extracted with ethyl acetate
  3. washwashed with saturated sodium hydrogen carbonate, brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed by evaporation
  6. customthe crude product was purified by preparative thin layer chromatography (10% methanol in chloroform)
  7. customto give free product
  8. stirringstirred at ambient temperature for 10 minutes
  9. customThe solvent was removed

Sources & evidence

ORD record
ord-1ae49a2af40d4f6d8b1fd76f77dc3aa1
Source dataset
uspto-grants-2001_04
Patent number
US06211242B1

Reaction notes

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