Diisopropylethylamine → (2R,3 S,5R)-5-((6-chloro-5-((4-(2-hydroxypropan-2-yl)phenyl)ethynyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

HRID 1050273Notes

Reaction equation

HRID 1050273 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([O:12][C@H:13]3[CH2:18][O:17][C@H:16]([CH2:19][OH:20])[C@@H:15]([OH:21])[CH2:14]3)=[N:9][C:5]2=[N:6][C:7]=1I.[C:22]([C:24]1[CH:29]=[CH:28][C:27]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=1)#[CH:23].C(N(C(C)C)CC)(C)C>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([O:12][C@H:13]3[CH2:18][O:17][C@H:16]([CH2:19][OH:20])[C@@H:15]([OH:21])[CH2:14]3)=[N:9][C:5]2=[N:6][C:7]=1[C:23]#[C:22][C:24]1[CH:29]=[CH:28][C:27]([C:30]([OH:33])([CH3:31])[CH3:32])=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 730124462-(4-Ethynylphenyl)propan-2-olHCID 90044277(2R,3S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

Product 1

HCID 90077302(2R,3 S,5R)-5-((6-chloro-5-((4-(2-hydroxypropan-2-yl)phenyl)ethynyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (2R,3 S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (50 mg, 0.120 mmol), 2-(4-ethynylphenyl)propan-2-ol (28.2 mg, 0.176 mmol), Pd(Ph3P)4 (13.58 mg, 0.012 mmol), copper(I) iodide (2.237 mg, 0.012 mmol) and diisopropylethylamine (0.062 ml, 0.360 mmol) in dioxane (2 ml) was charged in a reaction tube. Then the tube was sealed and N2 was bubbled through for 5 min. The mixture was heated at 80 C for 2 h, and then concentrated. The resulting residue was purified on reverse phase HPLC eluting with 10-70% CH3CN/H2O with TFA as an additive to give the title compound. LC-MS m/e=458.35 (M+H)+ (Rt 1.70/4.0 min); 1H NMR δ (ppm) (CD3OD): 7.83 (s, 1H), 7.58-7.54 (m, 4H), 5.13 (septet, 1H, J=5 Hz)), 4.34 (ddd 1H, J=12, 5, 2 Hz), 3.89 (dd, 1H, J=12, 2 Hz), 3.64 (dd, 1H, J=12, 6 Hz)), 3.61 (dd, 1H, J=12, 5 Hz), 3.37 (t, 1H, J=11 Hz), 3.19-3.15 (m, 1H), 2.77-2.73 (m, 1H), 1.70 (dd, 1H, J=23, 12 Hz), 1.55 (s, 6H).

Workup

  1. additionwas charged in a reaction tube
  2. customThen the tube was sealed
  3. customN2 was bubbled through for 5 min
  4. temperatureThe mixture was heated at 80 C for 2 h
  5. concentrationconcentrated
  6. customThe resulting residue was purified on reverse phase HPLC
  7. washeluting with 10-70% CH3CN/H2O with TFA as an additive

Sources & evidence

ORD record
ord-db30a1ae8a12467aa3d50794a3595a29
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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