Cesium carbonate → HCID 117842675, compound

HRID 2209156Notes

Reaction equation

HRID 2209156 reaction equation
O[CH2:2][CH2:3][N:4]1[C:8]2[C:9]([O:29][C@@H:30]([C@H:32]3[CH2:36][NH:35][C:34](=[O:37])[CH2:33]3)[CH3:31])=[N:10][C:11]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH2:24]CN(C5COC5)CC4)=[CH:15][CH:14]=3)=[CH:12][C:7]=2[N:6]=[CH:5]1.ClC1[N:44]=[C:43](O[C@@H]([C@H]2CNC(=O)C2)C)[C:42]2N(CCO)C=NC=2C=1.O1CC(N2CCN(C3C=CC(B4OC(C)(C)C(C)(C)O4)=CC=3)CC2)[CH2:61]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CO.ClCCl>[CH:3]1([N:4]2[C:8]3[C:9]([O:29][C@@H:30]([C@H:32]4[CH2:36][NH:35][C:34](=[O:37])[CH2:33]4)[CH3:31])=[N:10][C:11]([C:13]4[CH:18]=[C:17]5[C:16](=[CH:15][CH:14]=4)[N:19]([CH3:24])[N:44]=[C:43]5[CH3:42])=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:61][CH2:2]1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 117842921HCID 117842921, compoundHCID 117843550HCID 117843550, compoundHCID 123443518HCID 123443518, compound

Product 1

HCID 117842675HCID 117842675, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Preparation of (R)-4-((R)-1-((3-(2-hydroxyethyl)-6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: In a 25 mL sealed tube a mixture of (R)-4-((R)-1-((6-chloro-3-(2-hydroxyethyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one (85 mg, 0.26 mmol), 1-(oxetan-3-yl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine (108.12 mg, 0.31 mmol), Cesium Carbonate (255 mg, 0.78 mmol), & PEPPSI″-IPr catalyst (20 mg, 0.03 mmol) were taken up in dioxane (4 ml) and water (1 mL). and heated at 100° C. for 90 minutes. Chromatography on silica eluting with dichloromethane and methanol provided 28.1 mg of a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.25 (s, 1H), 8.01-7.91 (m, 2H), 7.71-7.57 (m, 2H), 7.05-6.95 (m, 2H), 5.82-5.64 (m, 2H), 4.63-4.34 (m, 6H), 3.69 (td, J=7.0, 3.5 Hz, 1H), 3.55-3.34 (m, 2H), 3.37-3.12 (m, 9H), 2.98 (p, J=7.9 Hz, 1H), 2.50-2.32 (m, 6H), 2.20 (dd, J=16.7, 7.0 Hz, 1H), 1.27-0.97 (m, 6H). ESI MS m/z 507 [M+H]+; HPLC, 1.24 min, 95.5% (AUC).

Workup

  1. customIn a 25 mL sealed tube

Sources & evidence

ORD record
ord-36d9e97c45bb4b66987a6b5424378c14
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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