Dichloromethane → 4-(4-amino-1-(1-(3-(3-fluorophenyl)-4-oxo-4H-chromen-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)thiophene-2-carbaldehyde

HRID 239696Notes

Reaction equation

HRID 239696 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[CH:32]([C:34]1[S:35][CH:36]=[C:37](B(O)O)[CH:38]=1)=[O:33].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>CN(C=O)C.C(O)C.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10]([C:37]3[CH:38]=[C:34]([CH:32]=[O:33])[S:35][CH:36]=3)[C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 110841152-Formylthiophene-4-boronic acidHCID 665799322-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one

Product 1

HCID 870715934-(4-amino-1-(1-(3-(3-fluorophenyl)-4-oxo-4H-chromen-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)thiophene-2-carbaldehydeYield 19.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 57c (0.350 g, 0.663 mmoles) in DMF (5 ml), ethanol (2.5 ml) and water (2.5 ml), 2-formyl-4-thiopheneboronic acid (0.155 g, 0.995 mmoles) and sodium carbonate (0.210 g, 1.98 mmoles) were added and the system is degassed for 30 min. Tetrakistriphenylphosphine Palladium (0.038 g, 0.033 mmoles) was added under nitrogen atmosphere and heated to 80° C. After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate. The organic layer 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 light brown solid (0.065 g, 19% yield). MP: 192-195° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 10.01(s,1H), 8.30(s,1H), 8.24(s,1H), 8.07(s,1H), 8.05(dd, J=7.9,1.4 Hz, 1H), 7.85(m,1H),7.69(d, J=8.4 Hz, 1H),7.53(t, J=7.8 Hz, 1H),7.28(br s,1H), 7.06(t, J=8.8 Hz, 1H),6.93(br s, 2H), 6.04(q, J=7.0 Hz, 1H),1.89(d, J=7.0 Hz, 3H). Mass: 511.95(M+).

Workup

  1. customthe system is degassed for 30 min
  2. concentrationconcentrated
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography with methanol

Sources & evidence

ORD record
ord-5a84b93fd4284f0e9ed6f0d8d4c736ec
Source dataset
uspto-grants-2014_02
Patent number
US08642607B2

Reaction notes

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