Diisopropylethylamine → HCID 178512400, compound

HRID 132570Notes

Reaction equation

HRID 132570 reaction equation
Cl.Cl.[NH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:23]=[CH:22][C:11]([O:12][CH2:13][C:14]([NH:16][C:17]2[NH:18][CH:19]=[CH:20][N:21]=2)=[O:15])=[CH:10][CH:9]=1.C(N(C(C)C)CC)(C)C.I.[NH2:34][C:35]1[C:36]([C:43]([NH:45][C:46](=[NH:49])SC)=[O:44])=[N:37][C:38]([Cl:42])=[C:39]([NH2:41])[N:40]=1>C(O)C.CO>[NH2:34][C:35]1[C:36]([C:43]([N:45]=[C:46]([NH2:49])[NH:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]2[CH:23]=[CH:22][C:11]([O:12][CH2:13][C:14]([NH:16][C:17]3[NH:21][CH:20]=[CH:19][N:18]=3)=[O:15])=[CH:10][CH:9]=2)=[O:44])=[N:37][C:38]([Cl:42])=[C:39]([NH2:41])[N:40]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 220544322-[4-(4-Aminobutyl)phenoxy]-N-(1H-imidazol-2-yl)acetamide dihydrochlorideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178512400HCID 178512400, compoundYield 32.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

A solution of 2-[4-(4-aminobutyl)phenoxy]-N-(1H-imidazol-2-yl)acetamide dihydrochloride 35 (99 mg, 0.27 mmol) and diisopropylethylamine (0.27 mL, 1.53 mmol) in absolute ethanol (4 mL) and anhydrous methanol (3 mL) was stirred at 70° C. for 30 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (130 mg, 0.34 mmol) was added in one portion. The reaction mixture was stirred for 3 h and then cooled to room temperature. The yellow insolubles were removed by suction filtration and the liquid filtrate was concentrated by rotary evaporation. The crude residue was purified by flash silica gel column chromatography eluting with dichloromethane/methanol/concentrated ammonium hydroxide (200:10:0,200:10:1, 150:10:1, and 100:10:1, v/v) to give 2-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}phenoxy)-N-(1H-imidazol-2-yl)-acetamide as a yellow solid (44 mg, 29% yield). The free base thus obtained was dissolved in methanol and treated with 4 drops of 4 N aqueous HCl. The solution was concentrated under reduced pressure and further dried under vacuum to give the final compound 36. mp 172-1740C. 1H NMR (300 MHz, CD3OD) δ 1.61-1.77 (m, 4H), 2.58-2.70 (m, 2H), 3.32-3.40 (m, 2H), 4.80 (s, 2H), 7.00 (d, 2H), 7.18 (d, 2H), 7.20 (s, 2H). m/z (ESI): 501 [C21H25ClN10O3+H]+.

Workup

  1. customThe yellow insolubles were removed by suction filtration
  2. concentrationthe liquid filtrate was concentrated by rotary evaporation
  3. customThe crude residue was purified by flash silica gel column chromatography
  4. washeluting with dichloromethane/methanol/concentrated ammonium hydroxide (200:10:0,200:10:1, 150:10:1, and 100:10:1

Sources & evidence

ORD record
ord-cba2fd503e1043a7b2730e93e8e02b26
Source dataset
uspto-grants-2008_06
Patent number
US07388013B2

Reaction notes

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