Diisopropylethylamine → HCID 178476577, compound

HRID 1696829Notes

Reaction equation

HRID 1696829 reaction equation
C(N(C(C)C)CC)(C)C.[C:10]([OH:13])(=[O:12])[CH3:11].[C:14]([OH:17])(=[O:16])[CH3:15].[OH:18][C:19]1[CH:24]=[CH:23][C:22]([C@@H:25]([OH:56])[CH2:26][N:27]([CH2:43][C@H:44]([OH:55])[C:45]2[CH:50]=[CH:49][C:48]([OH:51])=[C:47]([NH:52][CH:53]=[O:54])[CH:46]=2)[CH2:28][CH2:29][CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][CH2:40][CH2:41][NH2:42])=[CH:34][CH:33]=2)=[CH:21][C:20]=1[NH:57][CH:58]=[O:59].I.[NH2:61][C:62]1[C:63]([C:70]([NH:72][C:73](=[NH:76])SC)=[O:71])=[N:64][C:65]([Cl:69])=[C:66]([NH2:68])[N:67]=1>C(O)C>[C:10]([OH:13])(=[O:12])[CH3:11].[C:14]([OH:17])(=[O:16])[CH3:15].[OH:55][C@H:44]([C:45]1[CH:50]=[CH:49][C:48]([OH:51])=[C:47]([NH:52][CH:53]=[O:54])[CH:46]=1)[CH2:43][N:27]([CH2:26][C@@H:25]([C:22]1[CH:23]=[CH:24][C:19]([OH:18])=[C:20]([NH:57][CH:58]=[O:59])[CH:21]=1)[OH:56])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][CH2:39][CH2:40][CH2:41][NH:42][C:73]([NH:72][C:70]([C:63]2[C:62]([NH2:61])=[N:67][C:66]([NH2:68])=[C:65]([Cl:69])[N:64]=2)=[O:71])=[NH:76])=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86649685HCID 86649685, compoundHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178476577HCID 178476577, compoundYield 26.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Diisopropylethylamine (0.16 mL, 0.92 mmol) was added to a solution of {4-[4-(4-{bis-[2-(4-hydroxy-3-formylaminophenyl)-2-(R)-hydroxyethyl]amino}-butyl)phenyl]butyl}amine diacetic acid salt (13) (129 mg, 019 mmol) in absolute ethanol (4 mL). The mixture was stirred at 70° C. (oil bath) for 10 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (79 mg, 0.20 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 1% to 25%) to give the desired adduct 14 as a greenish yellow solid (44 mg, 26%): 1H NMR (500 MHz, DMSO-d6) δ 1.50 (m, 8H), 1.98 (s, 6H), 2.58 (m, 4H), 3.20 (m, 8H), 4.45 (m, 2H), 6.60 (br, 2H), 6.80 (m, 4H), 7.08 (m, 4H), 8.00 (s, 2H), 8.28 (s, 2H), 9.56 (br, 2H); m/z (ESI) 791 [C38H47ClN10O7+H]+; [α]D25 −4.0° (c 0.35, MeOH); mp 128-130° 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 1% to 25%)

Sources & evidence

ORD record
ord-cee82d1cf462402189ca273eddeea52a
Source dataset
uspto-grants-2012_04
Patent number
US08163758B2

Reaction notes

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