Dichloromethane → HCID 178434222, compound

HRID 1476243Notes

Reaction equation

HRID 1476243 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][C:19]([F:32])=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.C([N:40]1[C:48]2[C:43](=[CH:44][CH:45]=[C:46](B3OC(C)(C)C(C)(C)O3)[CH:47]=2)[C:42]([CH3:58])=[N:41]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]([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][C:19]([F:32])=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10]([C:46]3[CH:47]=[C:48]4[C:43]([C:42]([CH3:58])=[N:41][NH:40]4)=[CH:44][CH:45]=3)[C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53234609HCID 53234609, compoundHCID 58269235HCID 58269235, compound

Product 1

HCID 178434222HCID 178434222, compoundYield 11.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 57f (0.400 g, 0.733 mmoles) in DMF (5 ml), ethanol (2.5 ml) and water (2.5 ml), N-Boc-3-methyl-6-indazoleboronic acid pinacol ester 98 (0.393 g, 1.099 mmoles) and sodium carbonate (0.233 g, 2.19 mmoles) were added and the system is degassed for 30 min Tetrakistriphenylphosphine Palladium (0.043 g, 0.037 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 (0.045 g, 11% yield). MP: 234-236° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 12.75(s,1H), 8.06(s,1H), 7.86-7.70(m,4H), 7.61(s,1H), 7.33(m,2H), 7.06(dt, J=8.9,2.5 Hz, 1H), 6.87(m,2H), 6.07(q, J=7.0 Hz, 1H), 2.48(s,3H), 1.91(d, J=7.1 Hz, 3H). Mass: 549.95(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-1d4169c5bdcf417eba6c38ce817d9711
Source dataset
uspto-grants-2015_04
Patent number
US09018375B2

Reaction notes

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