Water → HCID 49783842, compound

HRID 1946842Notes

Reaction equation

HRID 1946842 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([S:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[Cl:21])=[C:7]([S:9](Cl)(=[O:11])=[O:10])[CH:8]=1)#[N:2].[CH3:22][N:23]([CH3:30])[CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.CCOC(C)=O.O>C(Cl)Cl>[Cl:21][C:15]1[CH:16]=[CH:17][C:18]([Cl:20])=[CH:19][C:14]=1[S:13][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][C:7]=1[S:9]([N:27]1[CH2:28][CH2:29][CH:24]([N:23]([CH3:30])[CH3:22])[CH2:25][CH2:26]1)(=[O:11])=[O:10]

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 417391N,N-Dimethylpiperidin-4-amineHCID 59548934HCID 59548934, compound

Product 1

HCID 49783842HCID 49783842, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of compound 29 (0.100 g, 0.26 mmol) in DCM (8.00 mL) was added 4-dimethylaminopiperidine (0.044 g, 0.34 mmol) and TEA (0.034 g, 0.34 mmol). The reaction was monitored with TLC (25% EtOAc in hexanes, Rf=0.0). After stirring at room temperature for 2 hrs, the reaction was complete as indicated by the absence of the starting material (TLC). Water was added and aqueous layer was extracted twice with DCM. Combined extracts were washed sequentially with water and brine, dried over MgSO4, filtered, and evaporated in vacuo to form a clear oil. The oil was dissolved in DCM and purified with chromatography with a gradient from 0 to 30% MeOH in DCM. Pure fractions were combined, evaporated in vacuo, triturated with DCM and hexanes, and then filtered to yield compound 83 as a white powder (0.068 g, 100% HPLC purity, 56% yield). 1H NMR (500 MHz, DMSO-d6): δ 8.26 (d, J=2 Hz, 1H), 7.89 (m, 2H), 7.78 (d, J=9 Hz, 1H), 7.71 (dd, J1=3 Hz, J2=9 Hz, 1H), 6.93 (d, J=8 Hz, 1H), 3.79 (d, J=12 Hz, 2H), 2.85 (t, J=13 Hz, 2H), 2.22 (m, 1H), 2.12 (s, 6H), 1.79 (m, 2H), 1.40 (m, 2H); MS (ESI, EI+): m/z=470 (MH+); melting point: 140-143° C.

Workup

  1. extractionaqueous layer was extracted twice with DCM
  2. washCombined extracts were washed sequentially with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto form a clear oil
  7. custompurified with chromatography with a gradient from 0 to 30% MeOH in DCM
  8. customevaporated in vacuo
  9. customtriturated with DCM and hexanes
  10. filtrationfiltered

Sources & evidence

ORD record
ord-cb2287a9070f407d931e5be72fbfad5e
Source dataset
uspto-grants-2013_03
Patent number
US08399456B2

Reaction notes

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