2-(Dimethylamino)ethanol → N-[4-(2-dimethylamino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-acetamide

HRID 540603Notes

Reaction equation

HRID 540603 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[CH:4][C:3]=1[C:12]1[N:13]([CH3:17])[N:14]=[CH:15][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:37][N:38]([CH3:42])[CH2:39][CH2:40]O.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:37][N:38]([CH3:42])[CH2:39][CH2:40][O:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[CH:4][C:3]=1[C:12]1[N:13]([CH3:17])[N:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 79022-(Dimethylamino)ethanolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 135697938N-(4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)phenyl)acetamide

Product 1

HCID 69494878N-[4-(2-dimethylamino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-acetamideYield 51.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-acetamide (0.85 g, 3.7 mmol) in THF (40 mL), triphenyl phosphine (2.91 g, 11.1 mmol) and 2-dimethylamino ethanol (1.11 mL, 11.1 mmol) were added followed by dropwise addition of diisopropyl azodicarboxylate (DIAD) (2.15 mL, 11.1 mmol). The reaction mixture was stirred at room temperature for 2 hours, concentrated to give a crude product that was subjected to a purification on preparative HPLC. The corresponding fractions were collected, neutralized with 1N NaOH and extracted with EtOAc four times to afford N-[4-(2-dimethylamino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-acetamide as a colorless waxy solid in 51.2% yield. LCMS m/z (%)=303 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ: 9.94 (s, 1H), 7.63 (d, J=8.93 Hz, 1H), 7.52 (s, 1H), 7.46 (s, 1H), 7.14 (d, J=8.98 Hz, 1H), 6.25 (s, 1H), 4.07 (t, J=5.82 Hz, 2H), 3.69 (s, 3H), 2.56 (t, J=5.80 Hz, 2H), 2.15 (s, 6H), 2.05 (s, 3H).

Workup

  1. concentrationconcentrated
  2. customto give a crude product that
  3. customwas subjected to a purification on preparative HPLC
  4. customThe corresponding fractions were collected
  5. extractionextracted with EtOAc four times

Sources & evidence

ORD record
ord-e591f40ab0534b79b3cd577cc346af1b
Source dataset
uspto-grants-2014_10
Patent number
US08871797B2

Reaction notes

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