Diisopropylethylamine → (R)-N-(4-((Difluoromethyl)thio)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinamide

A mixture of (R)-6-(3-hydroxypyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinic acid (Stage 170.1, 60 mg, 0.21 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 88 mg, 0.231 mmol) and DIPEA (73.2 μL, 0.419 mmol), in DMF (419 μL), was stirred at RT for 10 min. 4-Difluoromethylsulfanyl-aniline (60 mg, 0.21 mmol) was added and the RM was stirred for 2 days. The RM was diluted with EtOAc and washed with brine. The organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by preparative SFC (Column 2-EP, from 20% to 25% in 6 min) to obtain the title compound as a solid. UPLC-MS (Condition 3), tR=0.86 min, m/z=444.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6), δ ppm (TFA), 1.82 (br. s, 1H) 1.90 (d, J=8.60 Hz, 1H) 2.97 (d, J=10.95 Hz, 1H) 3.28 (d, J=7.04 Hz, 2H) 3.35-3.47 (m, 1H) 4.26 (br. s, 1H) 7.49-7.63 (m, 2H) 7.79-7.90 (m, 2H) 8.25 (br. s, 1H) 8.74 (br. s, 1H) 8.89-8.98 (m, 2H) 9.20-9.28 (m, 1H).

1. washwashed with brine
2. dry with materialThe organic phase was dried over MgSO4
3. customevaporated to dryness under reduced pressure
4. customThe crude product was purified by preparative SFC (Column 2-EP, from 20% to 25% in 6 min)

ORD-Eintrag

ord-4f16dbc755e3416aac5c14995cc44f9d

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09278981B2