Sodium hydride → HCID 57799832, compound

HRID 2101047Notes

Reaction equation

HRID 2101047 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]1[C:20]2[C:15](=[CH:16][C:17]([OH:21])=[CH:18][CH:19]=2)[CH:14]=[C:13]([NH:22][C:23]2[CH:27]=[C:26]([CH3:28])[NH:25][N:24]=2)[N:12]=1.Br[CH2:30][CH2:31][O:32][CH3:33]>CN(C)C=O.CO>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:21][CH2:30][CH2:31][O:32][CH3:33])=[CH:18][CH:19]=2)[CH:14]=[C:13]([NH:22][C:23]2[CH:27]=[C:26]([CH3:28])[NH:25][N:24]=2)[N:12]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 1360555241-(2,4-difluoro-phenyl)-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinolin-6-ol

Product 1

HCID 57799832HCID 57799832, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (17 mg, 60%) was added slowly to an ice-cooled solution of 1-(2,4-difluoro-phenyl)-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinolin-6-ol (150 mg) in 2 mL N,N-dimethylformamide (DMF). After stirred for 30 min, 1-Bromo-2-methoxy-ethane (59 mg) in 1 mL DMF was added cautiously by syringe. The mixture was warmed to room temperature and stirred overnight, then diluted with 1 mL methanol and directly sent to prep-HPLC. The product [1-(2,4-difluoro-phenyl)-6-(2-methoxy-ethoxy)-isoquinolin-3-yl]-(5-methyl-1H-pyrazol-3-yl)-amine (40 mg) was obtained as a yellow solid. LC-MS m/e 411(MH+). 1H NMR (400 MHz, DMSO) 9.12(s, 1H), 7.81(s, 1H), 7.61(m, 1H), 7.43(t, 1H), 7.34(d, 1H), 7.25(t, 1H), 7.10(d, 1H), 6.85(d, 1H), 5.81(s, 1H), 4.23(m, 2H), 3.71(m, 2H), 3.32(s, 3H), 2.20(s, 3H).

Workup

  1. stirringstirred overnight

Sources & evidence

ORD record
ord-f0f6ae22db78459f9394e219e380ac54
Source dataset
uspto-grants-2009_08
Patent number
US07572809B2

Reaction notes

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