2-[1-(2-amino-5-chloropyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol → (2R)-4-[1-(2-amino-5-chloropyrimidin-4-yl)-3-(2-hydroxypropan-2-yl)-1H-indazol-6-yl]-2-(5-meth yl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol

HRID 1398630Notes

Reaction equation

HRID 1398630 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](I)[CH:15]=3)[C:10]([C:18]([OH:21])([CH3:20])[CH3:19])=[N:9]2)[C:5]([Cl:22])=[CH:4][N:3]=1.[CH3:23][C:24]1[O:28][N:27]=[C:26]([C@:29]([OH:33])([C:31]#[CH:32])[CH3:30])[N:25]=1>N1CCCCC1.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>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:32]#[C:31][C@:29]([C:26]4[N:25]=[C:24]([CH3:23])[O:28][N:27]=4)([OH:33])[CH3:30])[CH:15]=3)[C:10]([C:18]([OH:21])([CH3:20])[CH3:19])=[N:9]2)[C:5]([Cl:22])=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 681818792-[1-(2-amino-5-chloropyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-olHCID 86669593(R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol

Product 1

HCID 68181624(2R)-4-[1-(2-amino-5-chloropyrimidin-4-yl)-3-(2-hydroxypropan-2-yl)-1H-indazol-6-yl]-2-(5-meth yl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8082PiperidineSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of 2-[1-(2-amino-5-chloropyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol (150 mg, 0.35 mmol) in piperidine (2 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (40.3 mg, 0.02 mmol), copper(I) iodide (6.6 mg, 0.02 mmol) and (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (106 mg, 0.70 mmol). The reaction was warmed to 35° C. for 1.5 hr. After cooling to RT, the reaction mixture was concentrated in vacuo and the residue purified by silica gel flash column chromatography (heptane/EtOAc gradient) to furnish the title compound as a dark red solid: 1H NMR (500 MHz, DMSO-d6) delta 1.69 (6H, s), 1.93 (3H, s), 2.69 (3H, s), 5.65 (1H, s), 6.85 (1H, s), 7.34 (2H, br. s.), 7.39 (1H, dd, J=8.35, 1.10 Hz), 8.21 (1H, d, J=8.35 Hz), 8.26 (1H, s), 8.51 (1H, s); LC-MS: m/z=+454.05/456.05 (M+H)+.

Workup

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue purified by silica gel flash column chromatography (heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-2bebcc2d4c1e4f1586575ac152e653c9
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

Loading…