Piperidine → 1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-N,N-dimethyl-1H-indazole-3-carboxamide

HRID 1398571Notes

Reaction equation

HRID 1398571 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]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1.N1CCCCC1.[S:29]1[CH:33]=[CH:32][N:31]=[C:30]1[C:34]([OH:38])([C:36]#[CH:37])[CH3:35]>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.C(Cl)Cl>[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]([OH:38])([C:30]4[S:29][CH:33]=[CH:32][N:31]=4)[CH3:35])[CH:15]=3)[C:10]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 8082PiperidineHCID 582215512-(Thiazol-2-yl)but-3-yn-2-olHCID 681822131-(2-aminopyrimidin-4-yl)-6-bromo-N,N-dimethylindazole-3-carboxamide

Product 1

HCID 601641681-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-N,N-dimethyl-1H-indazole-3-carboxamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a sealed tube was added 1-(2-aminopyrimidin-4-yl)-6-bromo-N,N-dimethylindazole-3-carboxamide (55%, 113 mg, 0.172 mmol), followed by piperidine (2 mL), tetrakis(triphenylphosphine)palladium (40 mg, 0.034 mmol), copper(I) iodide (7 mg, 0.034 mmol) and 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (105 mg, 0.688 mmol). The reaction mixture was purged with nitrogen gas, capped and stirred at 60° C. for 1.5 hr. Reaction mixture was concentrated in vacuo. EtOAc (5 mL) added. Concentration in vacuo was repeated. The residue was purified using column chromatography (Biotage, 100% DCM to 10% MeOH/DCM) to give a brown solid. Trituration of the solid with DCM gave the title compound: 1H NMR (500 MHz, DMSO) delta 1.95 (3H, s), 3.12 (3H, s), 3.33 (3H, s), 7.12 (2H, s), 7.13-7.19 (2H, m), 7.42 (1H, dd, J=8.35, 1.42 Hz), 7.71 (1H, d, J=3.31 Hz), 7.80 (1H, d, J=3.15 Hz), 7.97-8.07 (1H, m), 8.35 (1 H, d, J=5.52 Hz), 8.94 (1H, s); LC-MS: m/z=+434.45 (M+H)+.

Workup

  1. customThe reaction mixture was purged with nitrogen gas
  2. customcapped
  3. customReaction mixture
  4. concentrationwas concentrated in vacuo
  5. additionEtOAc (5 mL) added
  6. concentrationConcentration in vacuo
  7. customThe residue was purified
  8. customto give a brown solid

Sources & evidence

ORD record
ord-f0d639d4a59840419d16e60b17de5e43
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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