Piperidine → 4-((R)-2-methyl-1-thioureidopropyl)-N-(tetrahydro-2H-pyran-2-yloxy)benzamide

HRID 1049102Notes

Reaction equation

[NH2:1][C@@H:2]([C:6]1[CH:21]=[CH:20][C:9]([C:10]([NH:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)=[O:11])=[CH:8][CH:7]=1)[CH:3]([CH3:5])[CH3:4].C(N(CC)C(C)C)(C)C.C([N:48]=[C:49]=[S:50])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.N1CCCCC1>C(Cl)Cl>[CH3:4][CH:3]([CH3:5])[C@H:2]([C:6]1[CH:7]=[CH:8][C:9]([C:10]([NH:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)=[O:11])=[CH:20][CH:21]=1)[NH:1][C:49]([NH2:48])=[S:50]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 4-((R)-1-amino-2-methylpropyl)-N-(tetrahydro-2H-pyran-2-yloxy)benzamide (0.1643 g, 0.562 mmol) and N,N-diisopropylethylamine (0.1 mL, 0.6 mmol) in DCM (2.5 mL) was cooled in an ice bath and added to a solution of Fmoc-isothiocyanate (0.173 g, 0.616 mmol) in DCM (2.5 mL, 38 mmol) cooled at 0° C. in an ice bath. The reaction solution was stirred at rt for 1 h. Piperidine (1.0 mL, 2.0 mmol, 2.0 M in MeOH) was then added and the reaction stirred at rt for an additional 2 h. The reaction was concentrated and the residue was purified by flash chromatography (EtOAc:hex, 7:3 to 1:0) to afford 4-((R)-2-methyl-1-thioureidopropyl)-N-(tetrahydro-2H-pyran-2-yloxy)benzamide as a white solid. LC-MS: (FA) ES+ 352.

Workup

stirringthe reaction stirred at rt for an additional 2 h
concentrationThe reaction was concentrated
customthe residue was purified by flash chromatography (EtOAc:hex, 7:3 to 1:0)

Sources & evidence

ORD record: ord-97bb40d100134b4d985aec9ea8c6e28f
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382197B2

Reaction notes

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