Methanol → (R)-1-[5-(4-tert-Butyl-cyclohexyloxy)-benzothiazol-2-ylmethyl]-pyrrolidine-3-carboxylic acid

温度

0 °C

(R)-Pyrrolidine-3-carboxylic acid (100 mg, 0.9 mmol) (HCl salt) was combined with N,N-Diisopropylethylamine (300 uL, 2 mmol) in Methanol (4.0 mL, 98 mmol) and stirred for 15 min. 5-(4-tert-Butyl-cyclohexyloxy)-benzothiazole-2-carbaldehyde (10.0E2 mg, 0.33 mmol) was then added and the mixture was stirred at RT for 30 minutes. After 30 minutes the reaction was cooled to 0° C. and Sodium cyanoborohydride (100 mg, 2 mmol) was added in two portions. The reaction was then allowed to warm to RT while stirring overnight. The reaction was then purified directly on the Gilson (10-90% CH3CN/H2O (0.1% TFA), 19×150 cm C18, RT=8.6 min) The product was then dried on the highvac to give the title compound as a white solid. 1H NMR (400 MHz, MeOD) Shift=8.00-7.78 (m, 1H), 7.69-7.51 (m, 1H), 7.27-7.05 (m, 1H), 5.09-4.93 (m, 3H), 4.39-4.21 (m, 1H), 4.01-3.39 (m, 4H), 2.65-2.18 (m, 3H), 2.01-1.80 (m, 2H), 1.53-1.04 (m, 6H), 0.92 (s, 9H). MS (ESI, M+1): 417.30.

1. stirringthe mixture was stirred at RT for 30 minutes
2. temperatureto warm to RT
3. stirringwhile stirring overnight
4. customThe reaction was then purified directly on the Gilson (10-90% CH3CN/H2O (0.1% TFA), 19×150 cm C18, RT=8.6 min) The product
5. customwas then dried on the highvac

ORDレコード

ord-fa6f11a00a33478eb181dd103f6c1fc9

出典データセット

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09186367B2