Dichloromethane → HCID 69000188, compound

HRID 490094Notes

Reaction equation

HRID 490094 reaction equation
[NH2:1][C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[N:12]=[C:11]3[CH3:26])=[N:4][C:3]=1[N:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:50](Br)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.ClCCl>C1COCC1>[CH2:50]([NH:1][C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[N:12]=[C:11]3[CH3:26])=[N:4][C:3]=1[N:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 7498Benzyl BromideHCID 2733832Lithium HexamethyldisilazideHCID 69001720HCID 69001720, compound

Product 1

HCID 69000188HCID 69000188, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-amino-3-[N-(4-methoxybenzyl)-3-methylindazol-5-yl]-5-(4-Boc-piperazin-1-yl)-[1,2,4]triazine 111 (0.04 g, 0.0755 mmol) in anhydrous THF (2 mL), cooled at −78° C., was added a 1.0 M solution of lithium bis(trimethylsilyl)amide (0.083 mL) and benzyl bromide (0.001 mL dissolved in 0.1 mL THF). The reaction mixture was allowed to warm to room temperature. The reaction mixture was heated at 70° C. for 3 hours. Dichloromethane (50 mL) was added. The organic layer was washed with 1% citric acid, water and brine. The organic layer was dried over sodium sulfate. The organic solvent was evaporated under reduced pressure. The crude product was purified by RP-HPLC to yield the desired 6-benzylamino-3-[N-(4-methoxybenzyl)-3-methylindazol-5-yl]-5-(4-Boc-piperazin-1-yl)-[1,2,4]triazine 114 (0.027 g, 0.0435 mmol).

Workup

  1. temperatureThe reaction mixture was heated at 70° C. for 3 hours
  2. washThe organic layer was washed with 1% citric acid, water and brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customThe organic solvent was evaporated under reduced pressure
  5. customThe crude product was purified by RP-HPLC

Sources & evidence

ORD record
ord-19beec8f49474ad2bd913a8109f77303
Source dataset
uspto-grants-2009_05
Patent number
US07528132B2

Reaction notes

Loading…