Urea → HCID 58137344, compound

HRID 1424634Notes

Reaction equation

HRID 1424634 reaction equation
OC(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:22]=1[C:16]1([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)[N:15]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[C:14]2=[S:32].C([O-])([O-])=O.[K+].[K+].[CH:39]12[CH2:48][CH:43]3[CH2:44][CH:45]([CH2:47][CH:41]([CH2:42]3)[CH:40]1[N:49]=[C:50]=[O:51])[CH2:46]2.NC(N)=O>CC#N>[Cl:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:22]=1[C:16]1([CH2:21][CH2:20][N:19]([C:50]([NH:49][CH:40]3[CH:39]4[CH2:48][CH:43]5[CH2:44][CH:45]([CH2:47][CH:41]3[CH2:42]5)[CH2:46]4)=[O:51])[CH2:18][CH2:17]1)[N:15]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=1)[C:14]2=[S:32]

Participants

6

Reactant 4

HCID 1176UreaHCID 11430Potassium CarbonateHCID 128826302-IsocyanatoadamantaneHCID 86650842HCID 86650842, compound

Product 1

HCID 58137344HCID 58137344, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of crude 7-chloro-2-(4-methoxybenzyl)spiro[isoindoline-1,4′-piperidine]-3-thione TFA salt (prepared from TFA deprotection of tert-butyl 7-chloro-2-(4-methoxybenzyl)-3-thioxospiro[isoindoline-1,4′-piperidine]-1′-carboxylate (52 mg, 0.11 mmol)) in 1:1 MeCN:10% aq K2CO3 (10 mL), was added 2-adamantylisocyanate (50 mg, 0.30 mmol, 2.6 equiv) and the mixture stirred was for 2 h. After this time LC-MS analysis showed formation of the desired urea. The mixture was concentrated to ˜50% of its original volume and diluted with EtOAc. The mixture was washed with 1.0 M aq HCl and brine, dried over Na2SO4, and evaporated. The residue was purified by flash chromatography on silica gel (4 g), eluting with 20-80% EtOAc in hexanes, affording 7-chloro-N-(2-adamantyl)-2-(4-methoxybenzyl)-3-thioxospiro[isoindoline-1,4′-piperidine]-1′-carboxamide (51 mg, 0.093 mmol, 85% yield) of the desired thiolactam-urea as a pale yellow solid.

Workup

  1. concentrationThe mixture was concentrated to ˜50% of its original volume
  2. additiondiluted with EtOAc
  3. washThe mixture was washed with 1.0 M aq HCl and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe residue was purified by flash chromatography on silica gel (4 g)
  7. washeluting with 20-80% EtOAc in hexanes

Sources & evidence

ORD record
ord-55c26a4720044e608f61245ad9430f6e
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

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