Acetonitrile → HCID 178457835, compound

HRID 518672

Reaction equation

HRID 518672 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([N+:22]([O-:24])=[O:23])=[C:7]([NH:9][C@@H:10]2[CH2:15][CH2:14][C@H:13]([C:16]([NH:18][CH:19]([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH:8]=1.S(Cl)(Cl)=O.C(#N)C.[NH:32]1[CH2:37][CH2:36][CH:35]([C:38]([OH:41])([CH3:40])[CH3:39])[CH2:34][CH2:33]1>C(Cl)Cl.CO>[NH4+:9].[OH-:1].[OH:41][C:38]([CH:35]1[CH2:36][CH2:37][N:32]([CH2:2][C:3]2[CH:4]=[CH:5][C:6]([N+:22]([O-:24])=[O:23])=[C:7]([NH:9][C@@H:10]3[CH2:11][CH2:12][C@H:13]([C:16]([NH:18][CH:19]([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]3)[CH:8]=2)[CH2:33][CH2:34]1)([CH3:40])[CH3:39]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 24386Thionyl ChlorideHCID 52003212-(4-Piperidyl)-2-propanolHCID 178457837HCID 178457837, compound

Product 2

HCID 14923Ammonium HydroxideHCID 178457835HCID 178457835, compoundYield 180.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of cis-4-(5-(hydroxymethyl)-2-nitrophenylamino)-N-isopropylcyclohexanecarboxamide (3.75 g, 11.18 mmol) in DCM (127 mL) at 0° C. was added thionyl chloride (4.08 mL, 55.9 mmol) dropwise. The reaction was stirred at 0° C. for 3 hours and then at RT for 2 hours. The reaction was concentrated in vacuo and suspended in ACN and re-concentrated to remove residual thionyl chloride. The residue was resuspended in ACN (102 mL, 11.18 mmol), cooled to 0° C., and to it was added 2-(piperidin-4-yl)propan-2-ol (5.60 g, 39.1 mmol). The reaction was stirred at RT overnight. The mixture was filtered, and the filtrate concentrated in vacuo. The residual material was purified via silica gel chromatography, eluting with 90:10:1 DCM:MeOH:NH4OH to provide cis-4-(5-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-2-nitrophenylamino)-N-isopropylcyclohexanecarboxamide (4.64 g, 10.07 mmol, 90% yield) as an orange solid. MS m/z=461.4 [M+H], calc 460.61 for C25H40N4O4.

Workup

  1. waitat RT for 2 hours
  2. concentrationThe reaction was concentrated in vacuo
  3. concentrationre-concentrated
  4. customto remove residual thionyl chloride
  5. temperaturecooled to 0° C.
  6. stirringThe reaction was stirred at RT overnight
  7. filtrationThe mixture was filtered
  8. concentrationthe filtrate concentrated in vacuo
  9. customThe residual material was purified via silica gel chromatography
  10. washeluting with 90:10:1 DCM

Sources & evidence

ORD record
ord-c3cf6107a4c94976af1aae35b8a24af8
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Linked notes

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