HCID 68181728, compound → HCID 68181717, compound

HRID 1398613Notes

Reaction equation

HRID 1398613 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]([F:21])([CH3:20])[CH3:19])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.[CH3:22][C:23]1[O:27][N:26]=[C:25]([C@:28]([OH:32])([C:30]#[CH:31])[CH3:29])[N:24]=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>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:31]#[C:30][C@:28]([C:25]4[N:24]=[C:23]([CH3:22])[O:27][N:26]=4)([OH:32])[CH3:29])[CH:10]=3)[C:6]([C:18]([F:21])([CH3:20])[CH3:19])=[N:7]2)[CH:16]=[CH:15][N:14]=1

Participants

6

Reactant 2

HCID 68181728HCID 68181728, compoundHCID 86669593(R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol

Product 1

HCID 68181717HCID 68181717, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
66 °C

Procedure

To a solution of 4-[6-bromo-3-(2-fluoropropan-2-yl)-1H-indazol-1-yl]pyrimidin-2-amine (95 mg, 0.26 mmol) in piperidine (1 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (24 mg, 0.02 mmol), copper(I) iodide (4 mg, 0.02 mmol) and (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (79 mg, 0.52 mmol). The reaction mixture was warmed to 66° C. for 2 hr. After cooling to RT, the reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (Biotage, eluent:DCM containing a 1-10% MeOH gradient). Further purification by reverse phase preparative HPLC furnished the title compound as an orange solid: 1H NMR (500 MHz, DMSO) delta 1.76-2.00 (9H, m), 2.62 (3H, s), 6.82 (1H, s), 6.95-7.15 (3H, m), 7.39 (1H, d, J=9.93 Hz), 7.95 (1H, d, J=9.93 Hz), 8.33 (1H, br. s.), 8.94 (1H, s); LC-MS: m/z=+422.05 (M+H)+.

Workup

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue purified by flash chromatography (Biotage, eluent
  4. customFurther purification by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-150753d500b24a68b487426fd24bd1e2
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

Loading…