Reaktion #1752301

Reaktionsgleichung

3-(3-Isopropoxy-propylsulfamoyl)-benzoic acid

Intermediate V

3-(3-Isopropoxy-propylsulfamoyl)-benzoic acid

HATU

N-methyl morpholine

3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide dihydrochloride

→

title compound

3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [8-[3-(3-isopropoxy-propylsulfamoyl)-benzoyl]-1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide

Lösungsmittel

NaOH

NaOH

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction stirred at room temperature for 45 minutes
2. 2
   Extraktionthe crude product extracted into EtOAc (2×250 ml)
3. 3
   TrocknenThe organic phase is dried over MgSO4
4. 4
   Sonstigethe solvent evaporated in vacuo
5. 5
   Sonstigeto yield a yellow oil
6. 6
   SonstigePurification on a Waters preparative Delta 3000 HPLC
7. 7
   Sonstigeyields a yellow oil
8. 8
   Extraktionthe product is extracted into EtOAc (2×400 ml)
9. 9
   Trocknendried over MgSO4
10. 10
    Einengenthe solvent concentrated in vacuo to a volume of approximately 150 ml
11. 11
    workup.ADDITIONTo this solution is added iso-hexane (400 ml)
12. 12
    Sonstigea pale yellow solid precipitates
13. 13
    FiltrationThis solid is collected by filtration
14. 14
    Waschenrinsed with iso-hexane

Vorschrift

To a solution of 3-(3-Isopropoxy-propylsulfamoyl)-benzoic acid (Intermediate V) (1.10 g, 3.65 mmol) in DMF (20 ml) is added HATU (1.53 g, 4.02 mmol) and N-methyl morpholine (1.204 ml, 10.95 mmol) and the solution is stirred at room temperature for 5 minutes. 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide dihydrochloride (Ex. 38) (1.60 g, 4.02 mmol) is added and the reaction stirred at room temperature for 45 minutes. The reaction mixture is diluted with 2N NaOH (150 ml) and the crude product extracted into EtOAc (2×250 ml). The organic phase is dried over MgSO4 and the solvent evaporated in vacuo to yield a yellow oil. Purification on a Waters preparative Delta 3000 HPLC using a gradient of water (+0.1% TFA) and acetonitrile yields a yellow oil. 2N NaOH is added to the oil and the product is extracted into EtOAc (2×400 ml). The organic phases are combined, dried over MgSO4 and the solvent concentrated in vacuo to a volume of approximately 150 ml. To this solution is added iso-hexane (400 ml) and a pale yellow solid precipitates. This solid is collected by filtration and rinsed with iso-hexane to afford the title compound; [M+H]+ 607.98; 1H Nmr (DMSO): 1.00 (6H, d, J=6.0 Hz), 1.55 (2H, m), 1.69-1.79 (4H, m), 2.81 (2H, t, 5.9 Hz), 3.29 (2H, tr, J=6.0 Hz), 3.42 (1H, m), 3.44 (2H, br), 3.29-3.82 (4H, m), 6.15-7.30 (3H, br), 7.66 (1H, d, J=7.4 Hz), 7.70 (1H, dd, J=7.4 Hz, J=7.4 Hz), 7.76 (1H, s), 7.86 (1H, d, J=7.4 Hz), 7.44-8.00 (1H, br), 8.00-9.05 (3H, br).

Quelle