Piperidine → HCID 60164410, compound

HRID 1398715Notes

Reaction equation

HRID 1398715 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[C:13](N)=[CH:14][C:15]([F:18])=[C:16](Br)[C:11]=3[N:10]=[CH:9]2)[CH:5]=[CH:4][N:3]=1.N1CCCCC1.[CH3:26][C:27]([OH:31])([C:29]#[CH:30])[CH3:28]>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:12]3[CH:13]=[C:14]([C:30]#[C:29][C:27]([CH3:28])([OH:31])[CH3:26])[C:15]([F:18])=[CH:16][C:11]=3[N:10]=[CH:9]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 82582-Methyl-3-butyn-2-olHCID 68182096HCID 68182096, compound

Product 1

HCID 60164410HCID 60164410, compoundYield 26.7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
75 °C

Procedure

To a pressure tube was added 3-(2-aminopyrimidin-4-yl)-7-bromo-6-fluoro-1,3benzodiazol-4-amine (66%, 250 mg, 0.54 mmol), piperidine (1.5 mL), tetrakis(triphenylphosphine)palladium (61.9 mg, 0.05 mmol), copper(I) iodide (10.2 mg, 0.05 mmol) and 2-methylbut-3-yn-2-ol (0.1 ml, 1.07 mmol). The reaction was stirred at 75° C. for 2.5 h before concentrating in vacuo. The crude product was purified by column chromatography (Biotage) eluted with DCM: methanol gradient (98:3 to 90:10). Material obtained triturated with methanol to obtain the title compound as an off-white solid. (45 mg, 26.7% yield); 1H NMR (500 MHz, DMSO) delta 1.52 (6H, s), 5.53 (1H, s), 7.14 (1H, d, J=5.20 Hz), 7.18 (2H, br. s.), 7.67 (1H, d, J=9.62 Hz), 8.40 (1H, br. s.), 8.63 (1H, d, J=6.62 Hz), 9.16 (1H, s); LC-MS m/z+312.5 (M+H)+.

Workup

  1. concentrationbefore concentrating in vacuo
  2. customThe crude product was purified by column chromatography (Biotage)
  3. washeluted with DCM
  4. customMaterial obtained
  5. customtriturated with methanol

Sources & evidence

ORD record
ord-0a2bb3125fa147e0aa0b3b1b1a06f5f9
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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