Diisopropylethylamine → HCID 178448386, compound

HRID 2220969Notes

Reaction equation

HRID 2220969 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:15][C@@H:16]([CH:20]([CH3:22])[CH3:21])[C:17]([NH2:19])=[O:18])(=[O:14])=[O:13])=[CH:8][CH:7]=1.C(N(C(C)C)CC)(C)C.I.[NH2:33][C:34]1[C:35]([C:42]([NH:44][C:45](=[NH:48])SC)=[O:43])=[N:36][C:37]([Cl:41])=[C:38]([NH2:40])[N:39]=1>C(O)C>[NH2:33][C:34]1[C:35]([C:42]([N:44]=[C:45]([NH2:48])[NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]2[CH:7]=[CH:8][C:9]([S:12]([NH:15][C@@H:16]([CH:20]([CH3:22])[CH3:21])[C:17]([NH2:19])=[O:18])(=[O:14])=[O:13])=[CH:10][CH:11]=2)=[O:43])=[N:36][C:37]([Cl:41])=[C:38]([NH2:40])[N:39]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58649579(2S)-[4-(4-Aminobutyl)benzenesulfonylamino]-3-methylbutyramideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178448386HCID 178448386, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (2S)-[4-(4-aminobutyl)benzenesulfonylamino]-3-methylbutyramide 15 (156 mg, 0.47 mmol), diisopropylethylamine (0.60 mL, 3.0 mmol), and 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (230 mg, 0.61 mmol) in absolute ethanol (8 mL) was stirred at 70° C. for 5 h and then cooled to room temperature. The reaction mixture was concentrated by rotary evaporation. The crude residue was washed with water, filtered and the crude solid product was purified by flash silica gel column chromatography eluting with chloroform/methanol/concentrated ammonium hydroxide (5:1:0.1, v/v) to give the desired product as a yellow solid (137 mg, 54% yield). Part of the solid (86 mg) was further purified by semi-preparative HPLC (acetonitrile/water/0.1% TFA) to give the analytical pure sample which was then co-evaporated with 5% aqueous HCl to give the hydrochloride salt 16. mp 154-156° C. (decomposed). 1H NMR (300 MHz, CD3OD) δ 0.85 (d, 3H), 0.86 (d, 3H), 1.70 (m, 4H), 1.90 (m, 1H), 2.75 (m, 2H), 3.32 (m, 2H), 3.52 (d, 1H), 7.35 (d, 2H), 7.75 (d, 2H). m/z (ESI): 540 [C21H30ClN9O4S+H]+. [α]D25+5.2° (c 0.50, MeOH).

Workup

  1. concentrationThe reaction mixture was concentrated by rotary evaporation
  2. washThe crude residue was washed with water
  3. filtrationfiltered
  4. customthe crude solid product was purified by flash silica gel column chromatography
  5. washeluting with chloroform/methanol/concentrated ammonium hydroxide (5:1:0.1

Sources & evidence

ORD record
ord-5c7fcd1fe27948c7a8793666fe8dce31
Source dataset
uspto-grants-2008_05
Patent number
US07368451B2

Reaction notes

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