Dichloromethane → HCID 178434217, compound

HRID 239682Notes

Reaction equation

HRID 239682 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)C)[N:9]=[C:10](I)[C:3]=12.C([N:39]1[C:47]2[C:42](=[CH:43][CH:44]=[C:45](B3OC(C)(C)C(C)(C)O3)[CH:46]=2)[C:41]([CH3:57])=[N:40]1)(OC(C)(C)C)=O.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]([CH2:12][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)[N:9]=[C:10]([C:45]3[CH:46]=[C:47]4[C:42]([C:41]([CH3:57])=[N:40][NH:39]4)=[CH:43][CH:44]=3)[C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53234609HCID 53234609, compoundHCID 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 178434217HCID 178434217, compoundYield 20.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 57c (0.477 g, 0.930 mmoles) in DMF (5.3 ml), ethanol (2.6 ml) and water (2.6 ml), N-Boc-3-methyl-6-indazoleboronic acid pinacol ester 98 (0.500 g, 1.395 mmoles) and sodium carbonate (0.295 g, 3.318 mmoles) were added and the system is degassed for 30 min. Tetrakistriphenylphosphine Palladium (0.053 g, 0.046 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 off-white solid (0.100 g, 20% yield). MP: 246-248° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 12.75(s,1H), 8.22(s,1H), 8.06(dd, J=8.5,1.8 Hz, 1H), 7.84(d, J=8.3 Hz, 1H), 7.80(m,1H), 7.62(s,1H), 7.51(d, J=8.2 Hz, 2H), 7.39-7.31(m, 2H), 7.18(m, 2H), 7.12(dt, J=8.3,2.6 Hz, 1H), 5.56(s,2H), 2.51(s,3H). Mass: 517.51(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-5a2318d23ffe4d32b0bce67bc07992f8
Source dataset
uspto-grants-2014_02
Patent number
US08642607B2

Reaction notes

Loading…