Réaction #635896

Équation de réaction

3-[(9-Chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

ammonium formate

ammonium formate

→

title compound

Rendement 68.5%

3-[(4-Methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

Rendement 68.5%

Solvants

ethanol

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwas added
2. 2
   workup.ADDITIONwere added
3. 3
   Températurethe suspension heated for a further hour
4. 4
   FiltrationThe catalyst was filtered off
5. 5
   Autrethe volatiles removed in vacuo
6. 6
   Autreto give the crude product as a colourless oil
7. 7
   AutreThis residue was purified by reverse phase preparative HPLC
8. 8
   Lavageeluting with 5-95%

Mode opératoire

3-[(9-Chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide (150 mg, 0.29 mmol) was dissolved in ethanol (5 mL) and ammonium formate (147 mg, 2.33 mmol) was added in one portion. The reaction was blanketed with argon and 10% palladium on charcoal (10 mg) was added. The mixture was heated to 140° C. for a total of 55 minutes in a Smith Creator microwave reactor after which time a further 100 mgs of ammonium formate and 10 mgs of catalyst were added and the suspension heated for a further hour. The catalyst was filtered off and the volatiles removed in vacuo to give the crude product as a colourless oil. This residue was purified by reverse phase preparative HPLC, eluting with 5-95% acetoniltrile in water (+0.2% TFA), to give the title compound as a colourless foam (95 mg). 1H NMR δ (CDCl3): 2.12-2.19 (1H, m), 2.23-2.32 (1H, m), 3.23 (3H, s), 3.59 (2H, t), 3.88-3.91 (4H, m), 4.01 (3H, m), 4.42 (2H, t), 5.15-5.17 (1H, m), 6.61 (5H, d), 6.78-6.79 (1H, m), 6.80 (1H, t), 7.02 (1H, d), 7.33-7.36 (2H, m), 7.38-7.40 (1H, m), 7.85 (1H, d), 10.58 (1H, s); m/z 479 (M+H)+.

Source