Dimethylformamide → Imidazole

HRID 2303346Notes

Reaction equation

HRID 2303346 reaction equation
[Si](Cl)(C(C)(C)C)(C)C.[CH2:9]([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[CH3:10].ClCCl.C(#[N:21])C.CN(C=[O:26])C>CN(C)C1C=CN=CC=1>[NH:21]1[CH:13]=[CH:12][N:11]=[CH:9]1.[CH3:12][N:11]1[CH2:14][CH2:15][O:26][CH2:10][CH2:9]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 6342AcetonitrileHCID 6344DichloromethaneHCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chloride

Product 2

HCID 795ImidazoleHCID 79724-Methylmorpholine

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Conditions

Temperature
50 °C

Procedure

More specifically, a glycine methyl ester (8) is reacted with 2-nitrobenznesulfonyl chloride in accordance with an already known method, thereby obtaining a 2-nitrobenzenesulofonylated compound (9). The above-described chloro-derivative (6) is reacted with the compound (9) under the same conditions as described above to obtain a compound (10). The compound (10) is treated by an already known method, thereby obtaining a compound (11). The compound (11) is reduced by lithium aluminum hydride under the same conditions as described above, thereby obtaining an alcohol (12). The compound (12) is reacted with tert-butyldimethylsilyl chloride (TBDMS-Cl) at 0° C. to reflux temperature, preferably 50° C. for 1 hour to several days, preferably a night in the presence of a base such as imidazole, triethylamine or 4-methylmorpholine and 4-(dimethylamino)pyridine in a solvent dichloromethane, acetonitrile or DMF to obtain a TBDMS-derivative (13). The compound (13) is reacted with 9-fluorenylmethoxycarbonyl-amino acid (Fmoc-amino acid) (14) at 0° C. to reflux temperature, preferably room temperature for 1 minute to several days, preferably 10 minutes in the presence of a dehydration-condensing agent such as dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (water-soluble carbodiimide hydrochloride) or O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) in a solvent such as chloroform, dichloromethane, acetonitrile, THF, DMF or DMSO, thereby obtaining a compound (15). The compound (15) is reacted with piperidine in accordance with an already known method, thereby obtaining an amine derivative (16). The compound (16) is reacted with the above-described 2-nitrobenzenesulfonyl chloride under the same conditions as described above to obtain a 2-nitrobenzenesulfonylated compound (17). The compound (17) is treated by an already known method, thereby obtaining an alcohol (18). The compound (18) is dissolved in a solvent such as THF or dioxane and reacted with triphenylphosphine and diethyl azodicarboxylate (DEAD) at 0° C. to reflux temperature, preferably room temperature for 1 hour to several days, preferably a night, thereby obtaining a compound (19). The compound (19) is subjected to de-2-nitrobenzenesulfonylation by an already known method to obtain a compound (20). The above-described chloro-derivative (6) is reacted with the compound (20) under the same conditions as described above, thereby obtaining a compound (1b) according to the present invention.

Sources & evidence

ORD record
ord-19acc920f9e349eeb3af66eb08657774
Source dataset
uspto-grants-2002_08
Patent number
US06432957B1

Reaction notes

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