Dimethylformamide → HCID 22490316, compound

HRID 431549Notes

Reaction equation

Cl.[CH2:2]([O:9][NH2:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N([CH2:16][CH3:17])CC)C.O=C1CCC(=O)N1O[C:26](=[O:49])[CH2:27][CH:28]([C:34](=[O:48])[NH:35][CH:36]([C:40]([N:42]1[CH2:46][CH2:45][CH2:44][CH:43]1[CH3:47])=[O:41])[CH:37]([CH3:39])[CH3:38])[CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].CN(C)[CH:52]=[O:53]>>[CH2:2]([O:9][NH:10][C:26](=[O:49])[CH2:27][CH:28]([CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:34]([NH:35][CH:36]([C:40]([N:42]1[CH2:46][CH2:45][CH2:44][CH:43]1[CH2:47][O:53][CH2:52][C:17]1[CH:16]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:41])[CH:37]([CH3:38])[CH3:39])=[O:48])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

Reactant 4

HCID 6228Dimethylformamide2×

HCID 8471Triethylamine

HCID 102312Benzyloxyamine hydrochloride

HCID 87951564HCID 87951564, compound

Product 1

HCID 22490316HCID 22490316, compound

Procedure

The synthesis is comprised of the following steps: (a) a solution of 2-(S)-methylpyrrolidine hydrobromide 20 in dimethylformamide is treated with triethylamine followed by a solution of 2-tert-butoxycarbonylamino-3-methylbutyric acid 2,5-dioxo-pyrrolidin-1-yl 12 in dimethylformamide to yield (1-(2-methylpyrrolidine-1-carbonyl)-2-methyl-propyl)-carbamic acid tert-butyl ester 21; which is then (b) dissolved in methylene chloride, or any suitable solvent, and treated with trifluoroacetic acid to yield 2-amino-1-(2-methylpyrrolidin-1-yl)-3-methylbutan-1-one 22; (c) a solution of 22 in dimethylformamide is treated with triethylamine followed by a solution of 8 in dimethylformamide to yield 3-(1-(2-(S)-methylpyrrolidine-1-carbonyl)-2-(S)-methylpropyl-carbamoyl)-octanoic acid tert-butyl ester 23; (d) treatment of 23 in dichloromethane with trifluoroacetic acid to yield 3-(1-(2-methyl-pyrrolidine-1-carbonyl)-2-methyl-propylcarbamoyl)-octanoic acid 24; (e) treatment of a solution 24 and hydroxysuccinamide 7 with dicyclohexylcarbodiimide to afford 3-(1-(2-methyl-pyrrolidine-1-carbonyl)-2-methylpropylcarbamoyl)-octanoic acid 2,5-dioxo-pyrrolidin-1-yl ester 25; (f) treatment of a suspension of O-benzylhydroxyamine hydrochloride 18 in dimethylformamide with triethylamine followed by a solution of 25 in dimethylformamide to afford N4-benzyloxy-N1-(1-(2-benzyloxymethyl-pyrrolidine-1-carbonyl)-2-methyl-propyl)-2-pentyl-succinamide 26. (g) hydrogenating 26 with hydrogen gas and palladium in activated carbon wherein N4-hydroxy-N1-(1-(2-methyl-pyrrolidine-1-carbonyl)-3-methyl-propyl)-2-pentyl-succinamide 27 is thereby formed.

Sources & evidence

ORD record: ord-b68bacf196e640f29a56e3e12d08f438
Source dataset: uspto-grants-2003_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06660741B2

Reaction notes

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