2-Bromopropane → HCID 58328294, compound

HRID 544951Notes

Reaction equation

HRID 544951 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:25])=[C:11]([NH:13][C:14]([C:16]3[CH:24]=[C:23]4[C:19]([CH:20]=[CH:21][NH:22]4)=[CH:18][CH:17]=3)=[O:15])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.[H-].[Na+].[CH:28](Br)([CH3:30])[CH3:29]>CN(C=O)C>[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:25])=[C:11]([NH:13][C:14]([C:16]3[CH:24]=[C:23]4[C:19]([CH:20]=[CH:21][N:22]4[CH:28]([CH3:30])[CH3:29])=[CH:18][CH:17]=3)=[O:15])[CH:12]=2)=[O:6])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 63582-BromopropaneHCID 24758Sodium hydrideHCID 58328291HCID 58328291, compound

Product 1

HCID 58328294HCID 58328294, compoundYield 26.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-1H-indole-6-carboxamide (0.05 g, 0.15 mmol, example 94, table 5) in DMF (0.5 mL) was added sodium hydride (60% dispersion, 0.030 g, 0.75 mmol) over a period of 3 min, at room temperature. After stirring at room temperature for 5 min. isopropyl bromide (21 μL, 0.225 mmol) is added and the contents stirred at room temperature for 1 h. The reaction mixture was quenched with 100 μL of methanol and subjected to reverse phase preparative HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA). The desired fractions were collected, and concentrated using speedVac® Plus (SC250DDA) to yield the title compound (Example 224, 0.015 g). HPLC retention time (YMC S5 Combiscreen ODS; 4.6×50 mm (4 min. gradient); Solvent A=10% MeOH, 90% H2O, 0.2% H3PO4; solvent B=90% MeOH, 10% H2O, 0.2% H3PO4): 3.1 min. LCMS [M+H]+ 376.

Workup

  1. customat room temperature
  2. additionis added
  3. customThe reaction mixture was quenched with 100 μL of methanol
  4. customphase preparative HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)
  5. customThe desired fractions were collected
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-682f35bdc37540218a87a0fa07feca93
Source dataset
uspto-grants-2011_05
Patent number
US07935696B2

Reaction notes

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