Water → [2-(2-Bromo-4,5-difluorobenzyloxy)ethyl]dimethylamine

HRID 1631111Notes

Reaction equation

HRID 1631111 reaction equation
[Br:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]([F:17])=[CH:12][C:3]=1[CH2:4][O:5][CH2:6][CH2:7]CN(C)C.C(=O)([O-])[O-].[K+].[K+].O.N[C:26]1N=C(C(N2CC3C(=CC=CC=3)C2)=O)C2[C:28](=CC=C(B3OC(C)(C)C(C)(C)O3)C=2)[N:27]=1>C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]([F:17])=[CH:12][C:3]=1[CH2:4][O:5][CH2:6][CH2:7][N:27]([CH3:28])[CH3:26]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 58457219[2-Amino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanoneHCID 66836744[3-(2-Bromo-4,5-difluorobenzyloxy)propyl]dimethylamine

Product 1

HCID 66836629[2-(2-Bromo-4,5-difluorobenzyloxy)ethyl]dimethylamine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

88 mg of [3-(2-bromo-4,5-difluorobenzyloxy)propyl]dimethylamine, 80 mg of potassium carbonate, 5 μl of water and 12 mg of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride are added to a solution of 150 mg of [2-amino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone in 2 ml of ethanol under argon. The mixture is heated at 120° C. for 60 min. The solid is subsequently filtered off through kieselguhr with suction, and the filtrate is evaporated to dryness in vacuo. The residue is dissolved in 1 ml of DMSO and chromatographed by means of preparative HPLC (Agilent). The product fractions obtained are subsequently evaporated and freeze-dried.

Workup

  1. filtrationThe solid is subsequently filtered off through kieselguhr with suction
  2. customthe filtrate is evaporated to dryness in vacuo
  3. dissolutionThe residue is dissolved in 1 ml of DMSO
  4. customchromatographed by means of preparative HPLC (Agilent)
  5. customThe product fractions obtained
  6. customare subsequently evaporated
  7. customfreeze-dried

Sources & evidence

ORD record
ord-5e68aaf9068c484498d6a0125a443f18
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

Loading…