Cesium carbonate → HCID 178461585, compound

HRID 518621Notes

Reaction equation

HRID 518621 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([N:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][C@H:18]3[CH3:30])=[O:16])[CH2:11][CH2:10]2)[C:5]([N+:31]([O-:33])=[O:32])=[CH:4][N:3]=1.[N:34]1([CH2:40][CH2:41][OH:42])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.C1OCCOCCOCCOCCOCCOC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH3:30][C@H:18]1[N:17]([C:15]([C@H:12]2[CH2:13][CH2:14][C@@H:9]([NH:8][C:6]3[C:5]([N+:31]([O-:33])=[O:32])=[CH:4][N:3]=[C:2]([O:42][CH2:41][CH2:40][N:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)[CH:7]=3)[CH2:10][CH2:11]2)=[O:16])[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 18232N-PiperidinoethanolHCID 2855718-Crown-6HCID 178461583HCID 178461583, compound

Product 1

HCID 178461585HCID 178461585, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (R)-tert-butyl 4-(cis-4-(2-chloro-5-nitropyridin-4-ylamino)cyclohexanecarbonyl)-3-methylpiperazine-1-carboxylate (0.4 g, 0.830 mmol) in toluene (8.30 mL) was added 2-(piperidin-1-yl)ethanol (0.536 g, 4.15 mmol), 18-crown-6 (0.329 g, 1.245 mmol), and cesium carbonate (0.811 g, 2.490 mmol). The reaction was purged with argon and stirred at 75° C. overnight. The mixture was diluted with EtOAc to about 50 mL total volume and washed sequentially with water (50 mL), brine (50 mL), and aqueous NH4Cl (2×50 mL). The organic layer was dried over sodium sulfate and concentrated to afford an orange residue. The residue was purified by silica gel chromatography (1-5% MeOH/DCM, 1% NH4OH) to afford (R)-tert-butyl 3-methyl-4-(cis-4-(5-nitro-2-(2-(piperidin-1-yl)ethoxy)pyridin-4-ylamino)cyclohexanecarbonyl)piperazine-1-carboxylate as a tan solid (0.33 g, 69.2% yield). MS m/z=575.4 [M+H]. Calc'd for C29H46N6O6: 574.4.

Workup

  1. customThe reaction was purged with argon
  2. additionThe mixture was diluted with EtOAc to about 50 mL total volume
  3. washwashed sequentially with water (50 mL), brine (50 mL), and aqueous NH4Cl (2×50 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customto afford an orange residue
  7. customThe residue was purified by silica gel chromatography (1-5% MeOH/DCM, 1% NH4OH)

Sources & evidence

ORD record
ord-30d95a50381249ec970486c7322669e0
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

Loading…