Sodium Carbonate → Dactolisib

HRID 2199274Notes

Reaction equation

HRID 2199274 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3](B(O)O)[CH:2]=1.C([O-])([O-])=O.[Na+].[Na+].Br[C:21]1[CH:30]=[CH:29][C:28]2[N:27]=[CH:26][C:25]3[N:31]([CH3:46])[C:32](=[O:45])[N:33]([C:34]4[CH:39]=[CH:38][C:37]([C:40]([CH3:44])([CH3:43])[C:41]#[N:42])=[CH:36][CH:35]=4)[C:24]=3[C:23]=2[CH:22]=1>CN(C=O)C.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:44][C:40]([C:37]1[CH:36]=[CH:35][C:34]([N:33]2[C:24]3[C:23]4[CH:22]=[C:21]([C:3]5[CH:2]=[N:1][C:10]6[C:5]([CH:4]=5)=[CH:6][CH:7]=[CH:8][CH:9]=6)[CH:30]=[CH:29][C:28]=4[N:27]=[CH:26][C:25]=3[N:31]([CH3:46])[C:32]2=[O:45])=[CH:39][CH:38]=1)([CH3:43])[C:41]#[N:42]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734663Quinoline-3-boronic acidHCID 426095702-[4-(8-Bromo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl]-2-methylpropanenitrile

Product 1

HCID 11977753Dactolisib

Reagents, catalysts & solvents 2

HCID 178419050HCID 178419050, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

0.3 mmol of 3-quinoline boronic acid (Aldrich, Buchs, Switzerland), 8 mg of bis(triphenylphosphine)palladium (II) dichloride (Fluka, Buchs, Switzerland) and 0.5 ml of a 1 M solution of Na2CO3 are added to a solution of 84 mg (0.2 mmol) of 2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile (Example 1i) in 2 ml of DMF. The mixture is stirred for 1 h. at 100° C. After this time, the mixture is quenched with sat. aqueous NaHCO3 and extracted with EtOAc (2×). The organic layer is washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. The residue is loaded on silica gel and purified by flash chromatography to give the title compound. ES-MS: 470 (M+H)+; analytical HPLC: tret=2.90 min (Grad 1).

Workup

  1. customAfter this time, the mixture is quenched with sat. aqueous NaHCO3
  2. extractionextracted with EtOAc (2×)
  3. washThe organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-6a30c85225024725b6c115bd2d69dc8c
Source dataset
uspto-grants-2016_06
Patent number
US09358229B2

Reaction notes

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