Triphenylphosphine → methyl (4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)acetate

HRID 2373708Notes

Reaction equation

HRID 2373708 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[C:10]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[S:11][CH:12]=1.[NH:25]1[CH:29]=[C:28]([CH2:30][CH2:31]O)[CH:27]=[N:26]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[C:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:31][CH2:30][C:28]3[CH:29]=[N:25][NH:26][CH:27]=3)=[CH:15][CH:14]=2)[S:11][CH:12]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 42936042-(1H-Pyrazol-4-yl)ethanolHCID 86607176Methyl [4-(2-chlorophenyl)-2-(4-hydroxyphenyl)thien-3-yl]acetate

Product 1

HCID 86607181methyl (4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)acetateYield 92.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl [4-(2-chlorophenyl)-2-(4-hydroxyphenyl)thien-3-yl]acetate (0.485 g, 1.35 mmol), 2-(1H-pyrazol-4-yl)-ethanol (0.166 g, 1.48 mmol), and PPh3 (0.388 g, 1.4 mmol) in THF (3 mL) was added at 0° C. diethyl azo-dicarboxylate (DEAD) (0.265 g, 0.24 mL, 1.52 mmol). The solution was stirred overnight and the solvent removed. The product was purified directly by flash chromatography (20:1 CHCl3:MeOH) to yield methyl (4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)acetate (0.565 g). This material was reacted as in Example 1, Steps 7 and 8 to yield 2-(4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)-N-(diaminomethylene)acetamide (0.151 g) as a white solid. mp 71-72° C.; 1H NMR (500 MHz, DMSO-d6) δ: 2.90 (t, 2H, J=6.7 Hz), 3.50 (s, 2H), 4.15 (t, 2H, J=6.9 Hz), 7.05 (m, 2H), 7.44 (m, 6H), 7.55 (m, 2H), 7.70 (s, 1H). MS (ES) m/z 478.1 ([M−H]−). MS (ES) m/z 538.1 ([M+CH3COO]−). MS (ES) m/z 957.3 ([2M−H]−). Anal. Calcd for C24H22ClN5O2S.H2O: C, 57.88; H, 4.86; N, 14.06. Found: C, 55.49; H, 5.37; N, 14.80. A description of 2-(1H-pyrazol-4-yl)-ethanol can be found in Jones and Mann, J. Am. Chem. Soc., 75, 4048-52; 1953.

Workup

  1. customthe solvent removed
  2. customThe product was purified directly by flash chromatography (20:1 CHCl3:MeOH)

Sources & evidence

ORD record
ord-92405a358d994aa5926bde8a614b1bc8
Source dataset
uspto-grants-2008_12
Patent number
US07459567B2

Reaction notes

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