Triethylamine → HCID 178453774, compound

HRID 1175724Notes

Reaction equation

HRID 1175724 reaction equation
C(OC(=O)C)C.[C:7]([O:11][C:12]([NH:14][CH2:15][CH2:16][O:17][C:18](=[O:32])[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH2:29][CH2:30][NH2:31])=[CH:23][CH:22]=1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C(N(CC)CC)C.I.[NH2:41][C:42]1[C:43]([C:50]([NH:52][C:53](=[NH:56])SC)=[O:51])=[N:44][C:45]([Cl:49])=[C:46]([NH2:48])[N:47]=1>C1COCC1>[C:7]([O:11][C:12]([NH:14][CH2:15][CH2:16][O:17][C:18](=[O:32])[CH2:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:53]([NH2:56])=[N:52][C:50]([C:43]2[C:42]([NH2:41])=[N:47][C:46]([NH2:48])=[C:45]([Cl:49])[N:44]=2)=[O:51])=[CH:25][CH:26]=1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 67351832[4-(4-Aminobutyl)phenoxy]acetic acid 2-tert-butoxycarbonylaminoethyl ester ethyl acetateHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178453774HCID 178453774, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

A solution of [4-(4-aminobutyl)phenoxy]acetic acid 2-tert-butoxycarbonylaminoethyl ester ethyl acetate 45a (50 mg, 0.27 mmol) and triethylamine (0.27 mL, 1.53 mmol) in anhydrous THF (4 mL) was stirred at 55° C. (oil bath) for 15 min. To the solution was added 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (130 mg, 0.34 mmol) in two portions during a period of 15 min. The reaction mixture was stirred at 55° C. for 1 h and cooled to room temperature. The mixture 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, and 150:10:1, v/v) to give (4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl} phenoxy)acetic acid 2-tert-butoxycarbonylaminoethyl ester 46a (PSA 25309) as a yellow solid (60 mg, 76% yield). An analytical pure sample was obtained by semi-preparative HPLC purification (acetonitrile/water). mp 80-82° C. 1H NMR (300 MHz, CD3OD) δ 1.45 (s, 9H), 1.60-1.78 (m, 4H), 2.56-2.66 (m, 2H), 3.30-3.38 (m, 4H), 4.15-4.21 (m, 2H), 4.64 (s, 2H), 6.81 (d, 2H), 7.10 (d, 2H). m/z (ESI) 579 [C25H35ClN8O6+H]+.

Workup

  1. temperaturecooled to room temperature
  2. concentrationThe mixture 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, and 150:10:1

Sources & evidence

ORD record
ord-6b7720451cf84dd5a8f426139ac83662
Source dataset
uspto-grants-2010_11
Patent number
US07842697B2

Reaction notes

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