Triethylamine → N-(3,5-difluorobenzyl)-1-methyl-N-(2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro-[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethyl)cyclohexanecarboxamide

HRID 386610

Reaction equation

HRID 386610 reaction equation
[CH3:1][C:2]1([C:8]([OH:10])=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[Cl-].[F:25][C:26]1[CH:27]=[C:28]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:29][NH2+:30][CH2:31][C:32]([NH:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][C@@:39]1([C:47](=[O:48])[NH:46][C:45](=[O:49])[N:44]1[CH3:50])[CH2:38]2)=[O:33]>C(Cl)Cl.CN(C=O)C>[F:25][C:26]1[CH:27]=[C:28]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:29][N:30]([CH2:31][C:32]([NH:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][C@@:39]1([C:47](=[O:48])[NH:46][C:45](=[O:49])[N:44]1[CH3:50])[CH2:38]2)=[O:33])[C:8]([C:2]1([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)=[O:10]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 707441-Methylcyclohexanecarboxylic acidHCID 86647680N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethanaminium chloride2×

Product 1

HCID 25015785N-(3,5-difluorobenzyl)-1-methyl-N-(2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro-[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethyl)cyclohexanecarboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-methylcyclohexanecarboxylic acid (32.0 mg, 0.222 mmol) in DCM (1.5 mL) was added one drop of DMF (cat.), followed by oxalyl chloride (37.0 mg, 0.228 mmol), while at ambient temperature and under a constant stream of nitrogen. Upon cessation of gas evolution, the reaction mixture was cooled to 0° C. prior to the introduction of triethylamine (34.0 mg, 0.333 mmol) as a solution in DCM (2.0 mL), and then N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1′,3′-dihydrospiro[imidazolidine-4,2′-inden]-5′-yl]amino}-2-oxoethanaminium chloride (50.0 mg, 0.111 mmol, Intermediate 1). After 1 hour the reaction mixture was applied directly to a silica gel column for purification, eluting with DCM:MeOH—99:1 to 95:5. Product containing fractions were pooled and concentrated in vacuo to give the title compound. MS: m/z=561 (M+23(Na+)). HRMS: m/z=539.2477; calculated m/z=539.2464 for C29H33N4O4F2.

Workup

  1. customAfter 1 hour the reaction mixture was applied directly to a silica gel column for purification
  2. washeluting with DCM
  3. additionProduct containing fractions
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b6955718136e40a596cd15ee41e49d7c
Source dataset
uspto-grants-2013_02
Patent number
US08372859B2

Linked notes

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