Isobutyronitrile → HCID 57544703, compound

HRID 1254388Notes

Reaction equation

HRID 1254388 reaction equation
[Cl:1][C:2]1[C:3]([F:36])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][C@@H:25]([CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)[CH2:26][NH:27][CH3:28])=[O:23])[CH2:17]2)(O)[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1.[C:37](#[N:41])[CH:38]([CH3:40])[CH3:39].C([O-])([O-])=[O:43].[K+].[K+]>OS(O)(=O)=O.O>[Cl:1][C:2]1[C:3]([F:36])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][C@@H:25]([CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)[CH2:26][NH:27][CH3:28])=[O:23])[CH2:17]2)([NH:41][C:37](=[O:43])[CH:38]([CH3:40])[CH3:39])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6559IsobutyronitrileHCID 11430Potassium CarbonateHCID 44143403HCID 44143403, compound

Product 1

HCID 57544703HCID 57544703, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 1118Sulfuric AcidCatalyst

Procedure

(3R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-((S)-3-cyclohexyl-1-(methylamino)propan-2-yl)piperidine-1-carboxamide (70 mg, 0.133 mmol) was mixed with isobutyronitrile (8 mL) and conc H2SO4 (23 drops). After stirring vigorously overnight at rt, the mixture was neutralized with K2CO3 (ca. 100 mg). A few drops of water were added and the mixture was filtered. The filtrate was concentrated and the residue was purified by preparative HPLC to afford (3R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-(isobutyramido)-5-methoxypentyl)-N-((S)-3-cyclohexyl-1-(methylamino)propan-2-yl)piperidine-1-carboxamide (11.4 mg, 14%) as a TFA salt. 1H NMR (400 MHz, CDCl3): 7.94(s, 1H), 7.41(td, 1H), 7.27(td, 1H), 7.15(t, 1H), 4.25(d, 1H), 4.11(m, 1H), 3.92 (d, 1H), 3.37(t, 1H), 3.28(s, 3H), 3.07(dd, 1H), 2.96(dd, 1H), 2.71(s, 3H), 2.66(m, 1H), 2.54(td, 1H), 1.14(dd, 6H). 3 min. LC-MS: R/T 1.59 min., m/z 596 (M+H+). In addition, (3R)-3-((R)-1-(3-chloro-2-fluorophenyl)-1-(isobutyramido)-5-methoxypentyl)-N—((S)-3-cyclohexyl-1-(methylamino)propan-2-yl)piperidine-1-carboxamide and (S)-3-(1-(3-chloro-2-fluorophenyl)-5-methoxypent-1-enyl)-N-((S)-1-cyclohexyl-3-(methylamino)propan-2-yl)piperidine-1-carboxamide were isolated.

Workup

  1. filtrationthe mixture was filtered
  2. concentrationThe filtrate was concentrated
  3. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-d3f6afd0403f401187836759ee47552c
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

Loading…