(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-ol → (2R)-4-[1-(4-amino-1,3,5-triazin-2-yl)-2-methyl-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol

HRID 1398694Notes

Reaction equation

HRID 1398694 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH3:10])[N:7]([C:11]3[N:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=3)[C:6]=2[CH:18]=1.[CH3:19][C:20]1[O:24][N:23]=[C:22]([C@:25]([OH:29])([C:27]#[CH:28])[CH3:26])[CH:21]=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:14]=[CH:15][N:16]=[C:11]([N:7]2[C:6]3[CH:18]=[C:2]([C:28]#[C:27][C@:25]([C:22]4[CH:21]=[C:20]([CH3:19])[O:24][N:23]=4)([OH:29])[CH3:26])[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[CH3:10])[N:12]=1

Participants

6

Reactant 2

HCID 58221468(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-olHCID 681818904-(6-Bromo-2-methyl-benzoimidazol-1-yl)-[1,3,5]triazin-2-ylamine

Product 1

HCID 60164846(2R)-4-[1-(4-amino-1,3,5-triazin-2-yl)-2-methyl-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-olYield 39.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
95 °C

Procedure

To a solution of 4-(6-bromo-2-methyl-1,3-benzodiazol-1-yl)-1,3,5-triazin-2-amine (160 mg, 0.52 mmol) in piperidine (2 mL) was introduced tetrakis(triphenylphosphine)palladium(0) (60.59 mg, 0.05 mmol), copper(I) iodide (9.99 mg, 0.05 mmol) and (2R)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (118.9 mg, 0.79 mmol). The reaction was then warmed to 95° C. for 40 minutes (75 W, microwave heating). The reaction mixture was then cooled to RT and concentrated in vacuo. Purification of the residue by flash column chromatography (4-8% MeOH gradient in DCM) gave the title compound as a pale brown solid (77 mg): 1H NMR (500 MHz, DMSO) delta 1.81 (3H, s), 2.41 (3H, s), 2.90 (3H, s), 6.37 (1H, s), 6.51 (1H, s), 7.33 (1H, dd, J=8.28, 1.50 Hz), 7.60 (1H, d, J=8.20 Hz), 8.01 (1H, br. s.), 8.06 (1H, br. s.), 8.40 (1H, s), 8.66 (1H, s); LC-MS: m/z=+376.45 (M+H)+.

Workup

  1. temperature(75 W, microwave heating)
  2. temperatureThe reaction mixture was then cooled to RT
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by flash column chromatography (4-8% MeOH gradient in DCM)

Sources & evidence

ORD record
ord-18691c222c204161a506aed7e4b3d89a
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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