Piperidine → (2R)-4-[1-(4-amino-1,3,5-triazin-2-yl)-2-cyclopropyl-1H-1,3-benzodiazol-6-yl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol

HRID 1398696Notes

Reaction equation

HRID 1398696 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH:10]3[CH2:12][CH2:11]3)[N:7]([C:13]3[N:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=3)[C:6]=2[CH:20]=1.N1CCCCC1.[S:27]1[CH:31]=[CH:30][N:29]=[C:28]1[C@:32]([OH:36])([C:34]#[CH:35])[CH3:33]>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>[NH2:19][C:15]1[N:16]=[CH:17][N:18]=[C:13]([N:7]2[C:6]3[CH:20]=[C:2]([C:35]#[C:34][C@:32]([C:28]4[S:27][CH:31]=[CH:30][N:29]=4)([OH:36])[CH3:33])[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[CH:10]2[CH2:12][CH2:11]2)[N:14]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 58221813(r)-2-(Thiazol-2-yl)but-3-yn-2-olHCID 681815764-(6-Bromo-2-cyclopropyl-1,3-benzodiazol-1-yl)-1,3,5-triazin-2-amine

Product 1

HCID 68181598(2R)-4-[1-(4-amino-1,3,5-triazin-2-yl)-2-cyclopropyl-1H-1,3-benzodiazol-6-yl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

To a microwave vessel was added 4-(6-bromo-2-cyclopropyl-1,3-benzodiazol-1-yl)-1,3,5-triazin-2-amine (0.3 g, 0.91 mmol) followed by piperidine (2.5 mL), tetrakis(triphenylphosphine)palladium(0) (104.68 mg, 0.09 mmol), copper(I) iodide (17.25 mg, 0.09 mmol) and (2R)-2-(1,3-thiazol-2-yl)but-3-yn-2-ol (0.28 g, 1.81 mmol). The reaction was capped and stirred in the microwave at 95° C. for 25 minutes (55 W). The reaction mixture was cooled to RT and concentrated in vacuo. The residue was re-dissolved in EtOAc and re-evaporated in vacuo (twice). The crude residue was subjected to column chromatography (Biotage, 0-8% methanol gradient in DCM) and the partially purified product triturated with a mixture of EtOAc/heptane to give the title compound as a beige solid: 1H NMR (DMSO, 500 MHz) delta 1.06-1.20 (4H, m), 1.89 (3H, s), 3.24-3.29 (1H, m), 7.04 (1H, s), 7.30 (1H, dd, J=8.2, 1.4 Hz), 7.53 (1H, d, J=8.2 Hz), 7.69 (1H, d, J=3.2 Hz), 7.78 (1H, d, J=3.2 Hz), 8.05 (1H, s), 8.09 (1H, s), 8.29 (1H, s), 8.68 (1H, s); LC-MS: m/z=+400 (M+H)+.

Workup

  1. customThe reaction was capped
  2. temperatureThe reaction mixture was cooled to RT
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was re-dissolved in EtOAc
  5. customre-evaporated in vacuo (twice)
  6. customthe partially purified product triturated with a mixture of EtOAc/heptane

Sources & evidence

ORD record
ord-b581d6750db742c4bfcfbd51a4256836
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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