N-Methylpropylamine → N1-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-N3-methyl-N3-propylisophthalamide

Step 2 (A): (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution of 3-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acid (Step 1 (C), 60 mg, 0.088 mmol) in dichloromethane (2 mL) was added Hunig's base (34 mg, 0.267 mmol) to make a clear solution and HATU (45 mg, 0.12 mmol) was then added. After stirring for 20 min, the reaction mixture was added N-methylpropan-1-amine (13 mg, 0.178 mmol) and the reaction mixture was stirred at rt overnight. Ethyl acetate (100 mL) was added and the mixture was washed with Brine, H2O, dried and concentrated to give 55 mg of the title compound (85% yield): 1H NMR (CDCl3, 500 MHz) δ 0.02 (3H, s), 0.05 (3H, s), 0.71-0.76 (1H, m), 0.83 (9H, s), 0.87 (3H, m), 0.91-1.00 (2H, m), 1.40-1.53 (12H, m), 1.60-1.67 (1H, m), 2.01-2.05 (1H, m), 2.17-2.20 (1H, m), 2.64 (1H, m), 2.89-3.04 (4H, m), 3.17 (1H, brd s), 3.27-3.36 (3H, m), 3.48 (1H, brd s), 3.74 (1H, m), 3.97 (1H, m), 4.04-4.11 (2H, m), 4.58 (1H, m), 6.58 (1H, m), 6.76 (2H, d, J=5 Hz), 7.41-7.48 (2H, m), 7.86 (2H, s), 8.13 (1H, brd s).

1. additionwas then added
2. stirringthe reaction mixture was stirred at rt overnight
3. washthe mixture was washed with Brine, H2O
4. customdried
5. concentrationconcentrated

ORD-Eintrag

ord-63800b3d37ce42e28efc86010f5fda2e

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07745470B2