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

HRID 1398624Notes

Reaction equation

HRID 1398624 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](I)[CH:15]=3)[C:10]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[C:4]([NH:23][CH3:24])[N:3]=1.N1CCCCC1.[N:31]1[CH:36]=[CH:35][CH:34]=[N:33][C:32]=1[C:37]([OH:41])([C:39]#[CH:40])[CH3:38]>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(OCC)(=O)C.CCCCCCC>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:40]#[C:39][C:37]([OH:41])([C:32]4[N:33]=[CH:34][CH:35]=[CH:36][N:31]=4)[CH3:38])[CH:15]=3)[C:10]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[C:4]([NH:23][CH3:24])[N:3]=1

Participants

7

Reactant 3

HCID 8082PiperidineHCID 681818081-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-iodo-N,N-dimethyl-1H-indazole-3-carboxamideHCID 866695882-(Pyrimidin-2-yl)but-3-yn-2-ol

Product 1

HCID 681816351-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-[3-hydroxy-3-(pyrimidin-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 21899848Ethylacetate heptaneSolvent

Procedure

To a sealed tube was added 1-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-iodo-N,N-dimethyl-1H-indazole-3-carboxamide (86 mg, 0.20 mmol), followed by piperidine (2 mL), tetrakis(triphenylphosphine)palladium (23 mg, 0.02 mmol), copper(I) iodide (4 mg, 0.02 mmol) and 2-(pyrimidin-2-yl)but-3-yn-2-ol (58 mg, 0.39 mmol). The reaction mixture was purged with nitrogen gas, capped and stirred at room temperature for 1.5 hr. After cooling to RT, the reaction mixture was concentrated in vacuo. EtOAc (5 mL) was added and concentration in vacuo repeated. The residue was purified using column chromatography (Biotage, 0-10% gradient of methanol in DCM) to give a brown solid. Trituration of the solid with ethyl acetate/heptane gave the title compound. 1H NMR (DMSO, 500 MHz) delta 1.92 (3H, s), 2.80 (3H, d, J=4.1 Hz), 3.10 (3H, s), 3.31 (3H, s), 6.26 (2H, s), 6.49 (2H, s), 7.11 (1H, s), 7.30 (1H, d, J=8.4 Hz), 7.51 (1H, t, J=4.9 Hz), 7.94 (1H, d, J=8.4 Hz), 8.78-9.04 (3H, m); LC-MS: m/z=+458.10 (M+H)+.

Workup

  1. customThe reaction mixture was purged with nitrogen gas
  2. customcapped
  3. temperatureAfter cooling to RT
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. additionEtOAc (5 mL) was added
  6. concentrationconcentration in vacuo
  7. customThe residue was purified
  8. customto give a brown solid

Sources & evidence

ORD record
ord-e2ccff1fe8d440c99e4783d043d88a78
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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