Dichloromethane → 2-((4-amino-3-(3-hydroxyprop-1-ynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-one

HRID 1484336Notes

Reaction equation

HRID 1484336 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[O:14][C:15]4[C:20]([C:21](=[O:29])[C:22]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:9]=[C:10](I)[C:3]=12.[CH2:30]([OH:33])[C:31]#[CH:32].ClCCl>C1COCC1.[Cu]I>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[O:14][C:15]4[C:20]([C:21](=[O:29])[C:22]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:9]=[C:10]([C:32]#[C:31][CH2:30][OH:33])[C:3]=12

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 7859Propargyl alcoholHCID 582691472-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-one

Product 1

HCID 582691602-((4-amino-3-(3-hydroxyprop-1-ynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-oneYield 77%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 57a (0.180 g, 0.363 mmoles) in THF (5 ml), propargyl alcohol (0.051 g, 0.436 mmoles) diisopropylamine (0.31 ml, 1.81 mmoles), copper(I) iodide (7 mg, 0.036 mmoles) and) Tetrakis triphenylphosphine Palladium (0.042 g, 0.0363 mmoles) were added and the system is degassed for 30 min. and heated to reflux for 4 h. The reaction mixture filtered through celite pad and washed with ethyl acetate. The filtrate was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol:dichloromethane to afford the title compound as brown solid (0.118 g, 77% yield). MP: 171-173° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 8.21 (s, 1H), 8.06 (dd, J=7.9, 1.6 Hz, 1H), 7.77 (m, 1H), 7.50 (dt, J=8.0, 0.9 Hz, 1H), 7.40-7.33 (m, 6H), 5.43 (s, 2H), 4.33 (d, J=6.1 z, 2H). Mass: 423.88 (M+).

Workup

  1. customthe system is degassed for 30 min.
  2. temperatureheated
  3. temperatureto reflux for 4 h
  4. filtrationThe reaction mixture filtered through celite pad
  5. washwashed with ethyl acetate
  6. dry with materialThe filtrate was dried over sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography with methanol

Sources & evidence

ORD record
ord-63b49ba1fcdd4064b29ad9c44735a911
Source dataset
uspto-grants-2016_08
Patent number
US09421209B2

Reaction notes

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