Dichloromethane → HCID 178434216, compound

HRID 1476227Notes

Reaction equation

HRID 1476227 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.C([N:37]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43](B3OC(C)(C)C(C)(C)O3)[CH:44]=2)[C:39]([CH3:55])=[N:38]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: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:43]3[CH:44]=[C:45]4[C:40]([C:39]([CH3:55])=[N:38][NH:37]4)=[CH:41][CH:42]=3)[C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53234609HCID 53234609, compoundHCID 582691472-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-one

Product 1

HCID 178434216HCID 178434216, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 57a (0.462 g, 0.930 mmoles) in DMF (6 ml), ethanol (3 ml) and water (3 ml), N-Boc-3-methylindazole-6-boronic acid pinacol ester 98 (0.500 g, 1.39 mmoles) and sodium carbonate (0.295 g, 2.79 mmoles) were added and the system is degassed for 30 min Tetrakistriphenylphosphine Palladium (0.057 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 (0.120 g, 26% yield). MP: 2924-295° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 12.74(s,1H), 8.24(s,2H), 8.06(dd, J=7.9,1.5Hz, 1H), 7.84(d, J=8.3Hz, 1H), 7.75(m,1H), 7.63(s,1H), 7.49(t, J=7.3Hz, 1H), 7.45(d, J=8.3Hz, 1H), 7.38-7.32(m, 6H), 5.53(s, 2H), 2.51(s, 3H). Mass: 499.90(M+).

Workup

  1. additionwas added under nitrogen atmosphere
  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-ab6f08a79c0945e08cbbce35ab7bad97
Source dataset
uspto-grants-2015_04
Patent number
US09018375B2

Reaction notes

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