Cesium carbonate → HCID 86684750, compound

HRID 2401159Notes

Reaction equation

HRID 2401159 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:17][CH:18]4[CH:22]5[O:23][CH2:24][CH:25]([OH:26])[CH:21]5[O:20][CH2:19]4)[NH:16][C:11]3=[CH:10][C:9]=2[Cl:27])=[CH:4][CH:3]=1.[C:28]([CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)#[CH:29].C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I>[Cl:27][C:9]1[CH:10]=[C:11]2[NH:16][C:15]([O:17][C@H:18]3[C@H:22]4[O:23][CH2:24][C@@H:25]([OH:26])[C@H:21]4[O:20][CH2:19]3)=[N:14][C:12]2=[N:13][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([C:29]#[C:28][CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 52462504-ethynylpiperidineHCID 77462307HCID 77462307, compound

Product 1

HCID 86684750HCID 86684750, compound

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
50 °C

Procedure

3R,3aR,6R,6aR)-6-((5-(4-bromophenyl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (25 mg, 0.055 mmol), 4-ethynylpiperidine (10.5 mg, 0.072 mmol), copper (I) iodide (2.1 mg, 0.011 mmol), chloro(tri-tert-butyl)-2-[-(2′amino-1,1′-biphenyl)]palladium (II) (5.7 mg, 0.011 mmol, prepared by a procedure analogous to procedures described in J. AM. CHEM. SOC. 2010, 132, 14073-14075), and cesium carbonate (54.0 mg, 0.166 mmol) were placed under nitrogen in dry, degassed toluene (138 μl) and dimethylacetamide (138 μl). The mixture was stirred at 50° C. for 2 hours. The resulting residue was diluted with dimethylformamide (0.7 mL), then filtered through a filter disc (0.45 micron). The material was purified by reverse phase HPLC purification using 0-100% acetonitrile in water over 10 minutes. The desired product fraction was concentrated under reduced pressure to afford the title compound as an off-white solid. LC-MS: calculated for C25H25ClN4O4 480.16 observed m/e: 481.14 (M+H)+ (Rt 1.43/4 min). 1H NMR δ (ppm) (CD3OD): 7.80 (1H, s), 7.62 (2H, d, J=8.5 Hz), 7.49 (2H, d, J=8.5 Hz), 5.53 (1H, m), 4.95 (1H, t, J=5.5 Hz), 4.46 (1H, t, J=5.0 Hz), 4.27 (1H, m), 4.15 (1H, dd, J=9.5, 6.0 Hz), 4.09 (1H, dd, J=10.0, 4.9 Hz), 3.88 (1H, dd, J=8.0, 7.0 Hz), 3.58 (1H, t, J=8.5 Hz), 3.42 (2H, m), 3.18 (2H, m), 3.09 (1H, m), 2.17 (2H, m), 1.96 (2H, m)

Workup

  1. customin dry
  2. customdegassed toluene (138 μl) and dimethylacetamide (138 μl)
  3. additionThe resulting residue was diluted with dimethylformamide (0.7 mL)
  4. filtrationfiltered through a filter disc (0.45 micron)
  5. customThe material was purified by reverse phase HPLC purification
  6. customover 10 minutes
  7. concentrationThe desired product fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-314259c3c65e4e61a5b7a14c46f5951c
Source dataset
uspto-grants-2014_08
Patent number
US08796258B2

Reaction notes

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