Triethylamine → 7-Phenyl-isoquinoline-5-sulfonic acid {2-[2-(4-chloro-phenoxy)-ethylamino]-ethyl}-amide di-hydrochloride

HRID 2219230Notes

Reaction equation

HRID 2219230 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH:8]=O)=[CH:4][CH:3]=1.[ClH:12].Cl.[NH2:14][CH2:15][CH2:16][NH:17][S:18]([C:21]1[C:22]2[CH:23]=[CH:24][N:25]=[CH:26][C:27]=2[CH:28]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:30]=1)(=[O:20])=[O:19].CCN(CC)CC.[BH4-].[Na+]>CO>[ClH:1].[ClH:12].[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH2:8][NH:14][CH2:15][CH2:16][NH:17][S:18]([C:21]2[C:22]3[CH:23]=[CH:24][N:25]=[CH:26][C:27]=3[CH:28]=[C:29]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:30]=2)(=[O:20])=[O:19])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 114806982-(4-Chlorophenoxy)acetaldehydeHCID 866109257-Phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide di-hydrochloride

Product 1

HCID 695481677-Phenyl-isoquinoline-5-sulfonic acid {2-[2-(4-chloro-phenoxy)-ethylamino]-ethyl}-amide di-hydrochlorideYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A 1.96 mL of (4-chloro-phenoxy)-acetaldehyde stock solution (˜0.46 mmol) is added to a stirred mixture of 7-phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide di-hydrochloride (152 mg, 0.380 mmol), 4 Å molecular sieve (300 mg) and NEt3 (0.212 mL, 1.52 mmol) in anhydrous CH3OH (4 mL) at ambient temperature under nitrogen. The resultant mixture is stirred for 16 hours. Then the mixture is cooled to 0° C. before it is treated with powdered sodium borohydride (43.1 mg, 1.14 mmol). The mixture is stirred at 0° C. for 1 hour, then at ambient temperature for another 1 hour. After filtration and subsequent concentration in vacuo, the crude product is chromatographed on silica (gradient 5-25% CH3OH in EtOAc) to give 104 mg of the free amine product as a gum (0.216 mmol, 57% yield). The free amine (102 mg, 0.212 mmol) is dissolved in EtOAc (15 mL) and treated dropwise with 1N HCl/Et2O solution (0.635 mL) with stirring under nitrogen. The white suspension is stirred for 15 minutes, filtered and dried under vacuum at 60° C. to give 112 mg (0.202 mmol, 95% yield) of the title compound as a white powder. ESIMS: m/z 482 [(M+H)+, 35Cl], 484 [(M+H)+, 37Cl].

Workup

  1. waitat ambient temperature for another 1 hour
  2. filtrationAfter filtration and subsequent concentration in vacuo
  3. customthe crude product is chromatographed on silica (gradient 5-25% CH3OH in EtOAc)

Sources & evidence

ORD record
ord-094a59cbe33740039e95cacfab9342b2
Source dataset
uspto-grants-2008_08
Patent number
US07414063B2

Reaction notes

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