Water → 2-{3-[4-Amino-3-(4-aminophenyl)thieno[3,2-c]pyridin-7-yl]prop-2-ynyl}-1h-isoindole-1,3(2h)-dione

HRID 2390665Notes

Reaction equation

HRID 2390665 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[C:13]([NH2:18])=[N:14][CH:15]=[C:16](I)[C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:19]([N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32])[C:20]#[CH:21].O>COCCOC.C(N(CC)CC)C.[Cu]I>[NH2:18][C:13]1[C:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=3)=[CH:9][S:10][C:11]=2[C:16]([C:21]#[C:20][CH2:19][N:22]2[C:26](=[O:27])[C:25]3[C:24](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:23]2=[O:32])=[CH:15][N:14]=1

Participants

7

Reactant 3

HCID 962WaterHCID 81644N-prop-2-ynylphthalimideHCID 184507483-(4-Aminophenyl)-7-iodothieno[3,2-c]pyridin-4-amine

Product 1

HCID 184505472-{3-[4-Amino-3-(4-aminophenyl)thieno[3,2-c]pyridin-7-yl]prop-2-ynyl}-1h-isoindole-1,3(2h)-dioneYield 43.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of Example 77B (0.6 g, 1.63 mmol) in DME (3 mL) and triethylamine (2 mL) was degassed by bubbling nitrogen through the suspension for 5 minutes, treated with N-propargylphthalimide (0.45 g, 2.45 mmol), PdCl2(PPh3)4 (57 mg, 0.08 mmol), and CuI (15 mg, 0.08 mmol), then heated to 80° C. for 1 hour. The cooled solution was poured into water, extracted with ethyl acetate and the combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel using 3% methanol/dichloromethane to provide 300 mg (43% yield) of the desired product. 1H NMR (300 MHz, DMSO-D6) δ ppm 4.72 (s, 2H), 5.37 (s, 2H), 5.86 (s, 2H), 6.66 (d, J=8.14 Hz, 2H), 7.07 (d, J=8.14 Hz, 2H), 7.35 (s, 1H), 7.87-7.89 (m, 1H), 7.90 (s, 1H), 7.93 (d, J=4.07 Hz, 2H), 7.96 (d, J=5.76 Hz, 1H); MS (ESI(+)) m/e 425 (M+H)+

Workup

  1. customby bubbling nitrogen through the suspension for 5 minutes
  2. extractionextracted with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel using 3% methanol/dichloromethane

Sources & evidence

ORD record
ord-6eae29544cda49fcbda5752dd778e758
Source dataset
uspto-grants-2012_09
Patent number
US08273736B2

Reaction notes

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