Water → HCID 49784699, compound

HRID 1184378Notes

Reaction equation

HRID 1184378 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=2[CH3:21])=[C:7]([S:9](Cl)(=[O:11])=[O:10])[CH:8]=1)#[N:2].[NH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.CCOC(C)=O.O>ClCCl>[CH3:21][C:15]1[CH:16]=[CH:17][C:18]([CH3:20])=[CH:19][C:14]=1[O:13][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][C:7]=1[S:9]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)(=[O:11])=[O:10]

Participants

6

Reactant 4

HCID 962WaterHCID 4837PiperazineHCID 8857Ethyl AcetateHCID 59548935HCID 59548935, compound

Product 1

HCID 49784699HCID 49784699, compoundYield 41.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of sulfonyl chloride 32 (1.0 g, 3.1 mmol) in 20 mL dichloromethane was infused into a stirring solution of piperazine (5.9 g, 62.2 mmol) in 20 mL of dichloromethane at a rate of 0.2 mL/min. The reaction mixture was stirred for 16 hrs. The completion of the reaction was confirmed by TLC (25% EtOAc in hexanes). Water was then added and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were washed sequentially with water and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to produce a brown solid. The product was chromatographed on normal-phase silica using a gradient of 0-25% MeOH in dichloromethane. Desired fractions were collected and concentrated to produce compound 51 as a pink solid (0.5 g, 1.3 mmol). HPLC purity: 99%; 1H NMR (500 MHz, DMSO-d6): δ 8.22 (d, J=2 Hz, 1H), 7.99 (dd, J1=2 Hz, J2=8 Hz, 1H), 7.29 (d, J=8 Hz, 1H), 7.09 (d, J=8 Hz, 1H), 6.94 (s, 1H), 6.78 (d, J=8 Hz, 1H), 3.13 (m, 4H), 2.70 (m, 4H), 2.30 (s, 3H), 2.08 (s, 3H); MS (ESI, EI+): m/z=372 (MH+); melting point: 60-72° C.

Workup

  1. extractionthe aqueous layer was extracted twice with dichloromethane
  2. washThe combined organic layers were washed sequentially with water and brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto produce a brown solid
  7. customThe product was chromatographed on normal-phase silica using a gradient of 0-25% MeOH in dichloromethane
  8. customDesired fractions were collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-acbe9a99773b4fc492c529c37a351d53
Source dataset
uspto-grants-2014_03
Patent number
US08669247B2

Reaction notes

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