2-Hydrazinoethanol → HCID 135974913, compound

HRID 2075756Notes

Reaction equation

HRID 2075756 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]=[C:6](I)[C:5]2=O.[C:14]([C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1)#[CH:15].C(N(C(C)C)CC)(C)C.[OH:32][CH2:33][CH2:34][NH:35][NH2:36]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CC#N>[NH2:20][C:19]1[CH:21]=[CH:22][C:16]([C:14]#[C:15][C:6]2[C:5]([C:4]3[CH:3]=[C:2]([Cl:1])[CH:11]=[CH:10][C:9]=3[OH:8])=[N:36][N:35]([CH2:34][CH2:33][OH:32])[CH:7]=2)=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 80172-HydrazinoethanolHCID 81531DiisopropylethylamineHCID 37600254-EthynylanilineHCID 116666776-Chloro-3-iodochromone2×

Product 1

HCID 135974913HCID 135974913, compoundYield 69.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

To a mixture of 6-chloro-3-iodo-chromone (1A, 30.65 g, 0.1 mol), 4-ethynylaniline (14.05 g, 0.12 mol), PdCl2(PPh3)2 (1.404 g, 2.0 mmol) and CuI (190 mg, 1.0 mmol) was added anhydrous CH3CN (500 mL). Upon stirring, diisopropylethylamine (DIPEA, 69.7 mL, 0.4 mol) was added slowly to the above mixture. The reaction mixture was stirred at rt for 5 h. LCMS indicated all of 1A was consumed. 2-Hydroxyethylhydrazine (22 mL, 0.325 mol) was then added. The mixture was stirred at rt overnight. The mixture was filtered and the solid was washed with small amount of CH3CN, and dried under high vacuum to give 2A (8.1 g). Silica (˜100 mL) was added to the filtrate, and the solvent was removed with rotavapor. The resultant powder was load on a silica column and eluted with hexanes-ethyl acetate (v/v 2/1, 2/3, 1/1, 1/2) and then pure ethyl acetate. The fractions containing 2A were combined and solvent was removed. The residua were recrystallized from hexanes-ethyl acetate to give 2A (16.5 g). Total 24.6 g of the title compound 2A was obtained, and the yield is 69.5%. 1H NMR (CDCl3/CD3OD=5/1, 500 MHz) δ 8.71 (d, 1H, J=1.5 Hz), 7.80 (s, 1H), 7.39 (d, 2H, J=7.5 Hz), 7.19 (dd, 1H, J=8.0, 1.5 Hz), 6.95 (d, 1H, J=8.5 Hz), 6.70 (d, 2H, J=7.5 Hz), 4.28 (t, 2H, J=5.0 Hz), 3.98 (t, 2H, J=5.0 Hz). LCMS (ESI) m/z 354.17 (MH+, 100); HPLC: tR=4.05 min.

Workup

  1. stirringThe reaction mixture was stirred at rt for 5 h
  2. customwas consumed
  3. stirringThe mixture was stirred at rt overnight
  4. filtrationThe mixture was filtered
  5. washthe solid was washed with small amount of CH3CN
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-822e5f3cc10141e894544258d35e9f25
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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