2-Benzo[1,3]dioxol-5-ylmethyl-5-fluoro-7-(4-methyl-piperazin-1-yl)-benzo[d][1,3]oxazin-4-one → 5-Benzo[1,3]dioxol-5-ylmethyl-10-fluoro-8-(4-methyl-piperazin-1-yl)-[1,2,4]triazolo[1,5-c]quinazolin-2-ylamine

HRID 2039550Notes

Reaction equation

HRID 2039550 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][C:11]3O[C:13](=O)[C:14]4[C:20]([F:21])=[CH:19][C:18]([N:22]5[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]5)=[CH:17][C:15]=4[N:16]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.C(=O)(O)O.[NH2:34][NH:35][C:36]([NH2:38])=[NH:37]>N1C=CC=CC=1.O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][C:11]3[N:34]4[N:35]=[C:36]([NH2:38])[N:37]=[C:13]4[C:14]4[C:20]([F:21])=[CH:19][C:18]([N:22]5[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]5)=[CH:17][C:15]=4[N:16]=3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

5

Reactant 2

HCID 670426162-Benzo[1,3]dioxol-5-ylmethyl-5-fluoro-7-(4-methyl-piperazin-1-yl)-benzo[d][1,3]oxazin-4-oneHCID 178513185HCID 178513185, compound

Product 1

HCID 510379485-Benzo[1,3]dioxol-5-ylmethyl-10-fluoro-8-(4-methyl-piperazin-1-yl)-[1,2,4]triazolo[1,5-c]quinazolin-2-ylamineYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
180 °C

Procedure

To a suspension of 2-(2-benzo[1,3]dioxol-5-yl-acetylamino)-6-fluoro-4-(4-methyl-piperazin-1-yl)-benzoic acid methyl ester (0.15 g, 0.35 mmol) in a mixture of tetrahydrofuran (10 mL), methanol (1 mL) and water (2 mL), was added lithium hydroxide (0.15 g, 3.49 mmol). The reaction was stirred at room temperature overnight then the solvent was evaporated. The residue was diluted with water and 2 N HCl solution was added until pH 7. The solid precipitated was filtered and washed with water to obtain the 2-(2-benzo[1,3]dioxol-5-yl-acetylamino)-6-fluoro-4-(4-methyl-piperazin-1-yl)-benzoic acid crude. 2-(2-Benzo[1,3]dioxol-5-yl-acetylamino)-6-fluoro-4-(4-methyl-piperazin-1-yl)-benzoic acid was suspended in acetic anhydride (3 mL) and the reaction mixture was heated under microwave condition at 130° C. for 10 minutes. The solvent was evaporated to obtain the 2-benzo[1,3]dioxol-5-ylmethyl-5-fluoro-7-(4-methyl-piperazin-1-yl)-benzo[d][1,3]oxazin-4-one crude. To a solution of 2-benzo[1,3]dioxol-5-ylmethyl-5-fluoro-7-(4-methyl-piperazin-1-yl)-benzo[d][1,3]oxazin-4-one in dry pyridine (3 mL) was added aminoguanidine hydrogencarbonate (0.05 g, 0.39 mmol) and the mixture was heated under microwave condition at 180° C. for 15 minutes. The reaction was cooled at room temperature and diluted with water to induce the precipitation of a brown solid which was washed with a mixture MeOH/H2O 8/2, to afford the title compound (0.07 g, 46% yield).

Workup

  1. temperatureThe reaction was cooled at room temperature
  2. customthe precipitation of a brown solid which
  3. washwas washed with a mixture MeOH/H2O 8/2

Sources & evidence

ORD record
ord-426ff6e8cb4d4588a14ba7dcfa6587dc
Source dataset
uspto-grants-2013_11
Patent number
US08580783B2

Reaction notes

Loading…