Water → [2-Amino-6-[2-(hydroxymethyl)-4,5-dimethoxyphenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

HRID 1631110Notes

Reaction equation

HRID 1631110 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[CH2:12][OH:13].C(=O)([O-])[O-].[K+].[K+].O.[NH2:21][C:22]1[N:31]=[C:30]([C:32]([N:34]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:35]2)=[O:33])[C:29]2[C:24](=[CH:25][CH:26]=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:28]=2)[N:23]=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]>[NH2:21][C:22]1[N:31]=[C:30]([C:32]([N:34]2[CH2:35][C:36]3[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:42]2)=[O:33])[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([C:2]3[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=3[CH2:12][OH:13])[CH:28]=2)[N:23]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 618887(2-Bromo-4,5-dimethoxyphenyl)methanolHCID 58457219[2-Amino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

Product 1

HCID 56943447[2-Amino-6-[2-(hydroxymethyl)-4,5-dimethoxyphenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

48 mg of (2-bromo-4,5-dimethoxyphenyl)methanol, 80 mg of potassium carbonate, 7 μl of water and 8 mg of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride are added to a solution of 100 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 10 ml of ethanol under argon. The mixture is heated at 120° C. for 30 min. The solid is 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 prep. HPLC (Agilent). The product fractions obtained are subsequently evaporated and freeze-dried.

Workup

  1. filtrationThe solid is 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 prep
  5. customThe product fractions obtained
  6. customare subsequently evaporated
  7. customfreeze-dried

Sources & evidence

ORD record
ord-f5c04e586fc342f9a84c37433ea4078e
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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