Potassium Carbonate → (S)-4-(2-(4-fluorobenzylamino)-4-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-N-(2-(dimethylamino)ethyl)benzamide

HRID 1187276Notes

Reaction equation

HRID 1187276 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][NH:7][C:8]2[N:17]=[C:16]([O:18][C@H:19]3[CH2:23][CH2:22][O:21][CH2:20]3)[C:15]3[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:33][N:34]([CH3:49])[CH2:35][CH2:36][NH:37][C:38]([C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1)=[O:39]>CN(C=O)C.O>[F:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][NH:7][C:8]2[N:17]=[C:16]([O:18][C@H:19]3[CH2:23][CH2:22][O:21][CH2:20]3)[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:43]4[CH:44]=[CH:45][C:40]([C:38]([NH:37][CH2:36][CH2:35][N:34]([CH3:33])[CH3:49])=[O:39])=[CH:41][CH:42]=4)[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 44118750HCID 44118750, compoundHCID 59359761(S)-N-(4-fluorobenzyl)-6-bromo-4-(tetrahydrofuran-3-yloxy)quinazolin-2-amine

Product 1

HCID 59359767(S)-4-(2-(4-fluorobenzylamino)-4-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-N-(2-(dimethylamino)ethyl)benzamideYield 64.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(S)—N-(4-fluorobenzyl)-6-bromo-4-(tetrahydrofuran-3-yloxy)quinazolin-2-amine (50 mg, 0.12 mmol), potassium carbonate (33 mg, 0.24 mmol), tetrakis(triphenyl-phosphine)palladium (8 mg, 0.007 mmol) and 4-((2-(dimethylamino)ethyl)-carbamoyl)phenylboronic acid (36 mg, 0.132 mmol) in DMF (1.0 mL) and water (0.3 mL) was heated to 150° C. for 10 minutes under microwave irradiation. Solvents were concentrated in vacuo and the residue was purified by RP HPLC, using a C18 column with a gradient of 0.1% H2O, 0.1% TFA-acetonitrile, to provide the desired product (41 mg) which was characterized by its mass spectrum as follows: MS (m/z): 530 ([M+H]+, 100); HPLC Rt=1.26 minutes (Method B).

Workup

  1. concentrationSolvents were concentrated in vacuo
  2. customthe residue was purified by RP HPLC

Sources & evidence

ORD record
ord-6db9abb1b12c460b9fcf8f0c522ae975
Source dataset
uspto-grants-2014_03
Patent number
US08673929B2

Reaction notes

Loading…