Ethanolamine → (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-N-(2-hydroxyethyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxamide

To a solution of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid, Example 15 (90 mg, 0.20 mmol) in N,N-dimethylformamide (1 mL) was added 1-hydroxybenzotriazole (43 mg, 0.32 mmol), triethylamine (0.06 mL, 0.40 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (103 mg, 0.32 mmol). The solution was stirred for twenty-five minutes followed by addition of ethanolamine (0.02 mL, 0.32 mmol). The solution was stirred for twenty hours at ambient temperature. The reaction was quenched with water and the resulting yellow solid was collected by vacuum filtration. Chromatography (reverse phase, acetonitrile/water) provided (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-N-(2-hydroxyethyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxamide (yellow solid, 30 mg, 33% yield). LC/MS on 4.6×50 mm C-18 column, tR=6.00 minutes (10 to 90% acetonitrile/water over 6 minutes at 2 mL/minute with detection 254 nm, at 50° C.); ES-MS m/z 463 (M+H); HRMS Calculated for C26H27ClN4O2: 463.1895 (M+H)+. Found: 463.1875; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10-1.50 (m, 6H), 1.66-1.84 (m, 2H), 2.17-2.25 (m, 1H), 2.87-2.93 (m, 1H), 2.99-3.06 (m, 1H), 3.26-3.34 (m, 2H), 3.48 (t, J=6.18 Hz, 2H), 3.53-3.63 (m, 2H), 4.92 (dd, J=9.13, 6.18 Hz, 1H), 7.17 (dd, J=8.46, 1.75 Hz, 1H), 7.38 (d, J=2.15 Hz, 1H), 7.65 (d, J=8.86 Hz, 1H), 7.73 (d, J=8.59 Hz, 1H), 7.76 (s, 1H), 8.03 (d, J=8.06 Hz, 1H), 8.46 (t, J=6.31 Hz, 1H).

1. stirringThe solution was stirred for twenty hours at ambient temperature
2. customThe reaction was quenched with water
3. filtrationthe resulting yellow solid was collected by vacuum filtration

ORDレコード

ord-1c4855b0c0064751af85b6dd33042ee9

出典データセット

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07781428B2