Sodium hydride → HCID 25060727, compound

HRID 2244051Notes

Reaction equation

HRID 2244051 reaction equation
[CH3:1][C:2]1[C:10]2[C:9](=[O:11])[CH2:8][C:7]([CH3:13])([CH3:12])[CH2:6][C:5]=2[NH:4][CH:3]=1.[H-].[Na+].F[C:17]1[CH:26]=[C:25]2[C:20]([C:21]([NH2:28])=[N:22][C:23]([CH3:27])=[N:24]2)=[CH:19][CH:18]=1.C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[NH2:28][C:21]1[C:20]2[C:25](=[CH:26][C:17]([N:4]3[C:5]4[CH2:6][C:7]([CH3:13])([CH3:12])[CH2:8][C:9](=[O:11])[C:10]=4[C:2]([CH3:1])=[CH:3]3)=[CH:18][CH:19]=2)[N:24]=[C:23]([CH3:27])[N:22]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 248207983,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-oneHCID 25059433HCID 25059433, compound

Product 1

HCID 25060727HCID 25060727, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To 3,6,6,-trimethyl-1,5,6,7-tetrahydro-indol-4-one (0.3 g, 1.2 eq) in dimethylacetamide (50 mL) is added slowly sodium hydride (50.8 mg, 1.5 eq). The resulting mixture is stirred at RT for 0.5 h. To that 7-Fluoro-2-methyl-quinazolin-4-ylamine (0.25 g, 1 eq) is added and the mixture is stirred at 150° C. for overnight. The mixture is poured into sat'd NaHCO3 aq. solution (300 mL), and extracted by EtOAc (3×100 mL). The combined organic layers are dried over Na2SO4, filtered, concentrated. The crude product is purified by flash chromatography, eluted by 50% EtOAc in Hexane to EtOAc to give 1-(4-Amino-2-methyl-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one (0.135 g, 29% yield). LC/MS m/z=335 [M+H]+.

Workup

  1. stirringthe mixture is stirred at 150° C. for overnight
  2. extractionextracted by EtOAc (3×100 mL)
  3. dry with materialThe combined organic layers are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by flash chromatography
  7. washeluted by 50% EtOAc in Hexane to EtOAc

Sources & evidence

ORD record
ord-4102dfdfdc0841688909cd34b6d1b5da
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

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