Piperidine → 1-((S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)thiourea

HRID 1873916Notes

Reaction equation

HRID 1873916 reaction equation
[NH2:1][C@@H:2]([CH:22]([CH3:24])[CH3:23])[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=2)=[CH:13][N:14]=1)=[O:4].C([N:42]=[C:43]=[S:44])(=O)OCC1C2C=CC=CC=2C2C1=CC=CC=2.N1CCCCC1>C(Cl)Cl>[Br:21][C:18]1[CH:17]=[CH:16][C:15]([C:12]2[NH:11][C:10]([C@@H:6]3[CH2:7][CH2:8][CH2:9][N:5]3[C:3](=[O:4])[C@@H:2]([NH:1][C:43]([NH2:42])=[S:44])[CH:22]([CH3:24])[CH3:23])=[N:14][CH:13]=2)=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 8082Piperidine2×HCID 4154759Fmoc isothiocyanateHCID 57610942(S)-2-amino-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methylbutan-1-one

Product 1

HCID 576109411-((S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)thiourea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-amino-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methylbutan-1-one (1.530 g, 3.91 mmol) in CH2Cl2 (10 mL) was added O-(9H-fluoren-9-yl)methyl carbonisothiocyanatidate (1.100 g, 3.91 mmol) as a solid in one portion. The mixture was allowed to stir at room temperature for 12 h. Piperidine (2 mL) was added to the mixture and it was allowed to stir at room temperature for 1 h. A further portion of piperidine (2 mL) was added and the solution allowed to stir 1 h. The solution was concentrated to dryness and the residue was purified by column chromatography (biotage, eluting with 5:4.5:0.5 hex:EtOAc:MeOH, and then 5% MeOH in EtOAc). The title compound as obtained as a light yellow glass (1.30 g, 74%). 1HNMR (300 MHz, DMSO-d6) δ 11.81 (s, H), 7.65 (d, J=8.8 Hz), 7.63-7.71 (m, overlap with previous peak, 2H total), 7.42-7.56 (m, 2H), 7.10-7.14 (m, 1H), 5.06 (dd, J=7.0, 3.0 Hz, 1H), 4.94 (app t, J=8.0 Hz, 1H), 4.72-4.76 and 4.56-4.62 (m, 1H, rotamers, 1:1 ratio), 3.77-3.90 (m, 1H), 2.07-2.14 (m, 2H), 1.90-1.98 (m, 3H), 0.93 (d, J=7.0 Hz, 3H), 0.84 (d, J=7.0 Hz, 3H). LCMS: Anal. Calcd. for C19H24BrN5OS: 449, 451. found: 450, 452 (M+H)+.

Workup

  1. stirringto stir at room temperature for 1 h
  2. stirringto stir 1 h
  3. concentrationThe solution was concentrated to dryness
  4. customthe residue was purified by column chromatography (biotage
  5. washeluting with 5:4.5:0.5 hex

Sources & evidence

ORD record
ord-6d364cec8ffd488eadf94befbbe84dac
Source dataset
uspto-grants-2012_11
Patent number
US08303944B2

Reaction notes

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