1-(2-Hydroxyethyl)piperazine → HCID 178424515, compound

HRID 1508140Notes

Reaction equation

HRID 1508140 reaction equation
[CH3:1][C:2]1([CH3:28])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14](O)([CH3:16])[CH3:15])[CH:11]=[CH:10][C:9]=2[NH:18][C:19]([C:21]2[NH:22][CH:23]=[C:24]([C:26]#[N:27])[N:25]=2)=[O:20])=[CH:4][CH2:3]1.O=S(Cl)Cl.[OH:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.CCOC(C)=O>C(Cl)Cl>[CH3:1][C:2]1([CH3:28])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([N:39]3[CH2:40][CH2:41][N:36]([CH2:35][CH2:34][OH:33])[CH2:37][CH2:38]3)([CH3:16])[CH3:15])[CH:11]=[CH:10][C:9]=2[NH:18][C:19]([C:21]2[NH:22][CH:23]=[C:24]([C:26]#[N:27])[N:25]=2)=[O:20])=[CH:4][CH2:3]1

Participants

6

Reactant 4

HCID 76771-(2-Hydroxyethyl)piperazineHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 178424524HCID 178424524, compound

Product 1

HCID 178424515HCID 178424515, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-amide (as prepared in the previous step, 50.0 mg, 0.132 mmol) in 2 mL of DCM at −15° C. was added SOCl2 (29 μL, 0.40 mmol) under Ar. After stirring at RT for 1 h, the mixture was cooled back to −15° C. To the reaction was added 2-hydroxylethylpiperazine (162 μL, 1.32 mmol). After stirring at −15° C. for 1 h, the resulting mixture was warmed to RT and stirred for 16 h under Ar. Treated with EtOAc (30 mL), the mixture was washed with H2O (2×10 mL) and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (2-6% MeOH/DCM) to afford the title compound (37.5 mg, 58%) as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.12 (d, 1H, J=8.6 Hz), 7.93 (s, 1H), 7.42 (dd, 1H, J=8.6, 2.3 Hz), 7.34 (d, 1H, J=2.3 Hz), 5.72 (m, 1H), 3.70 (t, 2H, J=6.1 Hz), 2.52-2.77 (m, 10H), 2.25-2.32 (m, 2H), 2.04-2.10 (m, 2H), 1.59 (t, 2H, J=6.2 Hz), 1.38 (s, 6H), 1.08 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C28H38N6O2, 491.3 (M+H). found 491.0.

Workup

  1. temperaturethe mixture was cooled back to −15° C
  2. stirringAfter stirring at −15° C. for 1 h
  3. temperaturethe resulting mixture was warmed to RT
  4. stirringstirred for 16 h under Ar
  5. washthe mixture was washed with H2O (2×10 mL) and brine (10 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (2-6% MeOH/DCM)

Sources & evidence

ORD record
ord-ac8fd086f95f451ba2a100015bb0eb11
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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