Dichloromethane → HCID 178434218, compound

HRID 1484371Notes

Reaction equation

HRID 1484371 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][C:18]([F:30])=[CH:17][CH:16]=4)[N:9]=[C:10](I)[C:3]=12.C([N:38]1[C:46]2[C:41](=[CH:42][CH:43]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:45]=2)[C:40]([CH3:56])=[N:39]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][C:18]([F:30])=[CH:17][CH:16]=4)[N:9]=[C:10]([C:44]3[CH:45]=[C:46]4[C:41]([C:40]([CH3:56])=[N:39][NH:38]4)=[CH:42][CH:43]=3)[C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53234609HCID 53234609, compoundHCID 58269308HCID 58269308, compound

Product 1

HCID 178434218HCID 178434218, compoundYield 4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 57d (0.300 g, 0.584 mmoles) in DMF (3 ml), ethanol (1.5 ml) and water (1.5 ml), N-Boc-3-methyl-6-indazoleboronic acid pinacol ester 98 (0.314 g, 0.877 mmoles) and sodium carbonate (0.185 g, 1.754 mmoles) were added and the system is degassed for 30 min. Tetrakistriphenylphosphine Palladium (0.033 g, 0.029 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 brown solid (0.012 g, 4% yield). MP: 277-279° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 12.75 (s, 1H), 8.23 (s, 1H), 7.84 (d, J=8.2 Hz, 1H), 7.74 (dd, J=8.2, 3.0 Hz, 1H), 7.66 (m, 2H), 7.59 (dd, J=9.2, 4.2 Hz, 1H), 7.38-7.32 (m, 6H), 6.54 (s, 2H), 2.51 (s, 3H). Mass: 518.17 (M++1).

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-f49b5b39a0e44f1bab4a30393961d73d
Source dataset
uspto-grants-2016_08
Patent number
US09421209B2

Reaction notes

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