Diisopropylethylamine → HCID 178505028, compound

HRID 1696845Notes

Reaction equation

HRID 1696845 reaction equation
C([N:4](C(C)C)CC)(C)C.C(O)(=[O:12])C.C(O)(=O)C.[NH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][CH2:31][CH2:32][N:33]([CH2:49][C@H:50]([OH:63])[C:51]2[CH:56]=[CH:55][C:54]([OH:57])=[C:53]([NH:58][S:59]([CH3:62])(=[O:61])=[O:60])[CH:52]=2)[CH2:34][C@@H:35]([C:37]2[CH:38]=[CH:39][C:40]([OH:48])=[C:41]([NH:43][S:44]([CH3:47])(=[O:46])=[O:45])[CH:42]=2)[OH:36])=[CH:25][CH:24]=1.I.[NH2:65][C:66]1[C:67]([C:74]([NH:76][C:77](=[NH:80])SC)=[O:75])=[N:68][C:69]([Cl:73])=[C:70]([NH2:72])[N:71]=1>C(O)C>[OH-:12].[NH4+:4].[NH2:65][C:66]1[C:67]([C:74]([N:76]=[C:77]([NH2:80])[NH:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([CH2:29][CH2:30][CH2:31][CH2:32][N:33]([CH2:49][C@H:50]([OH:63])[C:51]3[CH:56]=[CH:55][C:54]([OH:57])=[C:53]([NH:58][S:59]([CH3:62])(=[O:60])=[O:61])[CH:52]=3)[CH2:34][C@@H:35]([C:37]3[CH:38]=[CH:39][C:40]([OH:48])=[C:41]([NH:43][S:44]([CH3:47])(=[O:46])=[O:45])[CH:42]=3)[OH:36])=[CH:27][CH:28]=2)=[O:75])=[N:68][C:69]([Cl:73])=[C:70]([NH2:72])[N:71]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 66859659HCID 66859659, compoundHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 2

HCID 14923Ammonium HydroxideYield 0.01%HCID 178505028HCID 178505028, compoundYield 23.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Diisopropylethylamine (0.33 mL, 1.89 mmol) was added to a solution of N-[5-(2-{{4-[4-(4-aminobutyl)phenyl]butyl}-[2-(R)-hydroxy-2-(4-hydroxy-3-methanesulfonyl-aminophenyl)ethyl]amino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]methanesulfonamide diacetic acid salt (41) (0.30 g, 0.375 mmol) in absolute ethanol (5 mL). The mixture was stirred at 70° C. (oil bath) for 15 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.16 g, 0.41 mmol) was added in one portion. The reaction mixture was stirred at that temperature for 3 h and cooled to rt. The solvent was removed by rotary evaporation. The residue was purified by Biotage silica gel column chromatography (A=dichloromethane, B=10% concentrated aqueous ammonium hydroxide in methanol, gradient B/A 0% to 25%), and further purified by preparative HPLC eluting with a gradient acetonitrile and water, each containing 0.01% concentrated ammonium hydroxide, to give the desired adduct 42 as a greenish yellow solid (78 mg, 23%): 1H NMR (500 MHz, DMSO-d6) δ 1.50 (m, 8H), 2.58 (m, 4H), 2.88 (s, 6H), 3.20 (m, 5H), 4.48 (m, 2H), 6.60 (br, 2H), 6.78 (d, 2H), 6.90 (d, 2H), 7.10 (s, 4H), 7.18 (s, 2H); m/z (ESI) 891 [C38H51ClN10O9S2+H]+; [α]D25 −23.0° (c 0.40, MeOH); mp 148-150° C.

Workup

  1. stirringThe reaction mixture was stirred at that temperature for 3 h
  2. temperaturecooled to rt
  3. customThe solvent was removed by rotary evaporation
  4. customThe residue was purified by Biotage silica gel column chromatography (A=dichloromethane, B=10% concentrated aqueous ammonium hydroxide in methanol, gradient B/A 0% to 25%), and
  5. customfurther purified by preparative HPLC
  6. washeluting with a gradient acetonitrile and water

Sources & evidence

ORD record
ord-7d5c8ceeb9ec4a2496b0062166b35b9c
Source dataset
uspto-grants-2012_04
Patent number
US08163758B2

Reaction notes

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