Piperidine → HCID 60164850, compound

HRID 1398603Notes

Reaction equation

HRID 1398603 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](Br)[CH:15]=3)[C:10]([C:18]([OH:21])([CH3:20])[CH3:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1.N1CCCCC1.[CH3:28][C:29]1[O:33][N:32]=[C:31]([C@:34]([OH:38])([C:36]#[CH:37])[CH3:35])[CH:30]=1>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:37]#[C:36][C@:34]([C:31]4[CH:30]=[C:29]([CH3:28])[O:33][N:32]=4)([OH:38])[CH3:35])[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 3

HCID 8082PiperidineHCID 58221468(R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-olHCID 68181837HCID 68181837, compound

Product 1

HCID 60164850HCID 60164850, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
65 °C

Procedure

To a pressure tube was added 2-[1-(2-aminopyrimidin-4-yl)-6-bromoindazol-3-yl]propan-2-ol followed by piperidine (2.5 mL), tetrakis(triphenylphosphine)palladium (102.88 mg, 0.09 mmol), copper(I) iodide (16.96 mg, 0.09 mmol) and (2R)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (269.16 mg, 1.78 mmol). The reaction was capped and stirred at 65° C. for 1.5 hr and then concentrated in vacuo. DCM (5 mL) was added to the reaction mixture and the concentration was repeated (×2). The crude product was purified by flash chromatography (Biotage, 1-10% methanol in DCM) gave the title compound: 1H NMR (500 MHz, DMSO) delta 1.63 (6H, s), 1.85 (3H, s), 2.41 (3H, s), 5.57 (1H, s), 6.41 (1H, s), 6.56 (1H, s), 7.00 (2H, s), 7.05 (1H, d, J=5.5 Hz), 7.33 (1H, dd, J=8.3, 1.2 Hz), 8.13 (1H, d, J=8.3 Hz), 8.27 (1H, d, J=5.2 Hz), 8.88 (1H, s); LC-MS: m/z=+419.10 (M+H)+.

Workup

  1. customThe reaction was capped
  2. concentrationconcentrated in vacuo
  3. additionDCM (5 mL) was added to the reaction mixture
  4. concentrationthe concentration
  5. customThe crude product was purified by flash chromatography (Biotage, 1-10% methanol in DCM)

Sources & evidence

ORD record
ord-4a1a71d4094d48fc8363dd07bde6722a
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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