Sodium hydride → HCID 74423574, compound

HRID 2244077Notes

Reaction equation

HRID 2244077 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+].[NH2:16][C:17]1[C:26]2[C:21](=[CH:22][C:23](F)=[CH:24][CH:25]=2)[C:20]([C:28](=[N:30][OH:31])[CH3:29])=[CH:19][N:18]=1.[NH4+].[Cl-]>CC(N(C)C)=O>[NH2:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([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:24][CH:25]=2)[C:20]([C:28](=[N:30][OH:31])[CH3:29])=[CH:19][N:18]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 248207983,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-oneHCID 74423706HCID 74423706, compound

Product 1

HCID 74423574HCID 74423574, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To 3,6,6,-trimethyl-1,5,6,7-tetrahydro-indol-4-one (0.104 g, 1.4 eq) in dimethylacetamide (3 mL), sodium hydride (14.4 mg, 1.4 eq) is added slowly and stirred at RT for 0.5 h. Then 1-(1-amino-6-fluoro-isoquinolin-4-yl)-ethanone oxime (90 mg, 1 eq) is added and the mixture is stirred at 150° C. overnight. The reaction is poured into Sat'd NH4Cl aq. (200 mL), extracted by EtOAc (3×100 mL), dried over Na2SO4, filtered, concentrated to give a crude product. That is purified by Biotage chromatography, eluted by 20% MeOH in DCM to give 1-(1-amino-4-(1-(hydroxyimino)ethyl)isoquinolin-6-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one (20 mg, 13%). LC/MS m/z=377 [M+H]+.

Workup

  1. stirringthe mixture is stirred at 150° C. overnight
  2. extractionextracted by EtOAc (3×100 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude product
  7. customThat is purified by Biotage chromatography
  8. washeluted by 20% MeOH in DCM

Sources & evidence

ORD record
ord-4f78082ad74043e49616e1f90d566a96
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

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