ChemicalBook CAS DataBase List Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate

Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate synthesis

13synthesis methods

Product Name:Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate
CAS Number:338992-20-4
Molecular formula:C26H30BrFN4O4
Molecular Weight:561.44

166815-96-9 Synthesis

N-TERT-BUTOXYCARBONYL-4-(4-TOLUENESULFONYLOXYMETHYL)PIPERIDINE

166815-96-9
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$7.00/250mg

Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate

338992-20-4
32 suppliers
$312.00/250mg

Yield:338992-20-4 86%

Reaction Conditions:

Stage #1: 4-(4-bromo-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazolinewith potassium carbonate in 1-methyl-pyrrolidin-2-one; for 0.166667 h;
Stage #2: N-tert-butoxycarbonyl-4-(4-toluenesulphonyloxymethyl)piperidine in 1-methyl-pyrrolidin-2-one at 95; for 3.5 - 4 h;Product distribution / selectivity;

Steps:

9; 10

7-hydroxy-4-(4-bromo-2-fiuoroanilino)-6-methoxyquinazoline (100 g) and potassium carbonate (113.8 g) were suspended in iV-methylpyrrolidinone (1070 ml) and stirred for 10 minutes prior to the addition of l-(fert-butoxycarbonyl)-4-(4- methylphenylsulfonyloxymethyl)piperidine (152.2 g). The reaction mixture was then heated to 95⁰C for 4 hours before being cooled back to 7O⁰C. Water (1922 ml) was then added over a period of 15 minutes. The reaction mixture was held at 73⁰C for 1 hour before being cooled to 4O⁰C and the product isolated by filtration. The product was washed with water (549 ml), slurry washed with ethyl acetate (549 ml) at 5O⁰C for 1 hour and then washed with ethyl acetate (275 ml) and dried at 50⁰C. Yield: 137 g, 86%; NMR Spectrum (DMSOd₆) 1.15-1.3 (m, 2H), 1.46 (s, 9H), 1.8 (d, 2H), 2.0-2.1 (m, IH), 2.65-2.9 (m, 2H) 3.95 (s, 3H), 4.02 (br s, 2H), 4.05 (d, 2H), 7.2 (s, IH), 7.48 (d, IH), 7.55 (t, IH), 7.65 (d, IH), 7.8 (d, IH), 8.35 (s, IH), 9.55 (br s, IH); Mass Spectrum [ESI] (M+H)⁺ = 561-563.; 7-hydroxy-4-(4-bromo-2-fluoroanilino)-6-methoxyquinazoline (5.0 g) and potassium carbonate (5.7 g) were suspended in N-methylpyrrolidinone (53.5ml) and stirred for 10 minutes. l-(tert-butoxycarbonyl)-4-(4-methylphenylsulfonyloxymethyl)piρeridine (7.6 g) was then added. The reaction mixture was then heated to 95⁰C and stirred at that temperature for 3.5 hours before being cooled back to 7O⁰C. Isopropanol (25 ml) was added and then water (75 ml) was added over a period of 15 minutes. The reaction mixture was then stirred at 73⁰C for 1 hour before cooling to 4O⁰C and isolation of the product by filtration. The product was washed with water (27.4 ml) and dried at 5O⁰C. Yield: 6.72 g, 87.2%; NMR Spectrum (DMSOd₆) 1.15-1.3 (m, 2H), 1.46 (s, 9H), 1.8 (d, 2H), 2.0-2.1 (m, IH), 2.65-2.9 (m, 2H) 3.95 (s, 3H), 4.02 (br s, 2H), 4.05 (d, 2H), 7.2 (s, IH), 7.48 (d, IH), 7.55 (t, IH), 7.65 (d, IH), 7.8 (d, IH), 8.35 (s, IH), 9.55 (br s, IH); Mass Spectrum [ESI] (M+H)⁺ = 561-563.