Dimethyl Sulfoxide → HCID 124000320, compound

HRID 1775022Notes

Reaction equation

HRID 1775022 reaction equation
F[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[C:21]([F:23])[CH:22]=4)[CH:15]=3)[N:10]([CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[NH:30]1[CH2:35][CH2:34][CH2:33][C@H:32]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[CH2:31]1.CS(C)=O>>[F:23][C:21]1[CH:22]=[C:17]([C:14]2[CH:15]=[C:16]3[C:8]([C:6]4[N:7]=[C:2]([N:30]5[CH2:35][CH2:34][CH2:33][C@H:32]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:41])([CH3:40])[CH3:42])[CH2:31]5)[CH:3]=[CH:4][CH:5]=4)=[N:9][N:10]([CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)[C:11]3=[CH:12][N:13]=2)[CH:18]=[N:19][CH:20]=1

Participants

4

Reactant 3

HCID 679Dimethyl SulfoxideHCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 71253531HCID 71253531, compound

Product 1

HCID 124000320HCID 124000320, compound

Conditions

Temperature
95 °C

Procedure

A solution containing 3-(6-fluoropyridin-2-yl)-5-(5-fluoropyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (0.055 g, 0.14 mmol) and (S)-tert-butyl piperidin-3-ylcarbamate (0.196 g, 0.979 mmol) in Dimethyl sulfoxide (0.840 mL, 11.8 mmol) was heated at 95° C. for 18 h. The reaction was quenched with water and then extracted with EtOAc 2×. The combined organic layer was dried with Na2SO4, filtered and concentrated. The crude product was dried under high vacuum overnight to give tert-butyl (3S)-1-(6-(5-(5-fluoropyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-3-ylcarbamate which was dissolved in 1,4-Dioxane (1.50 mL, 19.2 mmol) and treated with 4.0 M of Hydrogen chloride in 1,4-Dioxane (2.50 mL). The reaction was stirred at RT for 18 h. The reaction was concentrated then submitted for rHPLC to give 206 (37.8 mg, 69% yield). ESI MS m/z=390.1 (M+1). 1H NMR (400 MHz, DMSO) δ 9.22 (s, 1H), 9.18 (s, 1H), 9.03 (s, 1H), 8.60 (d, J=2.7 Hz, 1H), 8.32 (d, J=10.3 Hz, 1H), 7.66 (t, J=8.0 Hz, 1H), 7.45 (d, J=7.4 Hz, 1H), 6.87 (d, J=8.5 Hz, 1H), 4.37-4.25 (m, 2H), 3.08-2.96 (m, 1H), 2.85-2.75 (m, 2H), 2.00-1.88 (m, 1H), 1.85-1.75 (m, 1H), 1.68-1.56 (m, 1H), 1.42-1.25 (m, 1H)

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with EtOAc 2×
  3. dry with materialThe combined organic layer was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dry with materialThe crude product was dried under high vacuum overnight

Sources & evidence

ORD record
ord-e369ef56befe4642b95eb39c0da35a8e
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

Loading…