2-(Pyridin-2-yl)but-3-yn-2-ol → 4-[1-(2-aminopyrimidin-4-yl)-3-(2-hydroxypropan-2-yl)-1H-indazol-6-yl]-2-(pyridin-2-yl)but-3-yn-2-ol

HRID 1398605Notes

Reaction equation

HRID 1398605 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)[CH:5]=[CH:4][N:3]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]([OH:32])([C:30]#[CH:31])[CH3:29]>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:31]#[C:30][C:28]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][N:22]=4)([OH:32])[CH3:29])[CH:15]=3)[C:10]([C:18]([OH:21])([CH3:20])[CH3:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 167625022-(Pyridin-2-yl)but-3-yn-2-olHCID 681818982-[1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol

Product 1

HCID 681820824-[1-(2-aminopyrimidin-4-yl)-3-(2-hydroxypropan-2-yl)-1H-indazol-6-yl]-2-(pyridin-2-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-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol (150 mg, 0.36 mmol) in piperidine (2 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (16.8 mg, 0.02 mmol), copper(I) iodide (2.8 mg, 0.02 mmol) and 2-(pyridin-2-yl)but-3-yn-2-ol (112 mg, 0.73 mmol). The reaction was warmed to 35° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (Biotage, DCM containing a 1-10% MeOH gradient) to furnish the title compound as a brown oil: 1H NMR (500 MHz, CDCl3) delta 1.78 (6H, s), 1.94 (3H, s), 2.84 (1H, br. s.), 5.18 (2H, br. s.), 5.80 (1H, br. s.), 7.19-7.39 (1H, m), 7.74 (1H, d, J=7.88 Hz), 7.82 (1H, td, J=7.72, 1.58 Hz), 7.90 (1H, d, J=8.35 Hz), 8.29 (1H, d, J=5.36 Hz), 8.58 (1H, d, J=4.73 Hz), 8.89 (1 H, s); LCMS: m/z=+415.05 (M+H)+.

Workup

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue purified by flash chromatography (Biotage, DCM containing a 1-10% MeOH gradient)

Sources & evidence

ORD record
ord-741c529d00254a91b8aad825fc16853b
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

Loading…