Sodium hydride → 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1-(2-(dimethylamino)-2-oxoethyl)-1H-indol-5-yl)cyclopropanecarboxamide

HRID 1847877Notes

Reaction equation

HRID 1847877 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][CH:24]=4)[NH:21][CH:20]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[H-].[Na+].Cl[CH2:32][C:33]([N:35]([CH3:37])[CH3:36])=[O:34]>CN(C=O)C.C1COCC1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][CH:24]=4)[N:21]([CH2:32][C:33]([N:35]([CH3:37])[CH3:36])=[O:34])[C:20]([C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 758862-chloro-N,N-dimethylacetamideHCID 591292381-(Benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butylindolin-5-yl)cyclopropanecarboxamide

Product 1

HCID 591293071-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1-(2-(dimethylamino)-2-oxoethyl)-1H-indol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butylindolin-5-yl)cyclopropanecarboxamide (62 mg, 0.16 mmol) in anhydrous DMF (0.11 mL) and THF (1 mL) was added NaH (60% in mineral oil, 21 mg, 0.51 mmol) at room temperature under N2. After 30 min of stirring, the reaction mixture was cooled to 0° C. and 2-chloro-N,N-dimethylacetamide (11 mL, 0.14 mmol) was added. The reaction mixture was stirred for 5 min at 0° C. and then for 10 h at room temperature. The mixture was purified by preparative HPLC and the resultant solid was dissolved in DMF (0.6 mL) in the presence of Pd—C (10 mg). The mixture was stirred open to the atmosphere overnight at room temperature. The reaction mixture was filtrated and purified by preparative HPLC providing 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1-(2-(dimethylamino)-2-oxoethyl)-1H-indol-5-yl)cyclopropanecarboxamide. MS (ESI) m/e (M+H+) 462.0.

Workup

  1. stirringThe reaction mixture was stirred for 5 min at 0° C.
  2. waitfor 10 h at room temperature
  3. customThe mixture was purified by preparative HPLC
  4. dissolutionthe resultant solid was dissolved in DMF (0.6 mL) in the presence of Pd—C (10 mg)
  5. stirringThe mixture was stirred open to the atmosphere overnight at room temperature
  6. filtrationThe reaction mixture was filtrated
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-d100396da97d44839fea0c10def5cbca
Source dataset
uspto-grants-2015_02
Patent number
US08952049B2

Reaction notes

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