Piperidine → 4-[1-(2-aminopyrimidin-4-yl)-1H-indazol-6-yl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol

HRID 1398478Notes

Reaction equation

HRID 1398478 reaction equation
I[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.N1CCCCC1.[S:24]1[CH:28]=[CH:27][N:26]=[C:25]1[C:29]([OH:33])([C:31]#[CH:32])[CH3:30]>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>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:32]#[C:31][C:29]([C:25]4[S:24][CH:28]=[CH:27][N:26]=4)([OH:33])[CH3:30])[CH:10]=3)[CH:6]=[N:7]2)[CH:16]=[CH:15][N:14]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 582215512-(Thiazol-2-yl)but-3-yn-2-olHCID 681817324-(6-iodo-1H-indazol-1-yl)pyrimidin-2-amine

Product 1

HCID 601639044-[1-(2-aminopyrimidin-4-yl)-1H-indazol-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

Procedure

To a mixture of 4-(6-iodo-1H-indazol-1-yl)pyrimidin-2-amine (1-a1) (150 mg, 0.285 mmol) and piperidine (1 mL) was added tetrakis(triphenylphosphine)palladium (49.3 mg, 0.043 mmol), copper(I) iodide (8.1 mg, 0.043 mmol) and 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (I-1) (131 mg, 0.854 mmol). The reaction was purged with N2 and stirred at RT for 30 min. The reaction mixture was concentrated in vacuo and the residue purified by reverse phase preparative HPLC to afford the title compound: 1H NMR (500 MHz, DMSO) δ 1.95 (3H, s), 7.04 (2H, br. s.), 7.08-7.13 (2H, m), 7.35 (1H, dd, J=8.20, 1.26 Hz), 7.70 (1H, d, J=3.15 Hz), 7.79 (1H, d, J=3.15 Hz), 7.89 (1H, d, J=8.51 Hz), 8.30 (1H, d, J=5.67 Hz), 8.50 (1H, s), 8.91 (1H, s). LC-MS: m/z=+363.4 (M+H)+.

Workup

  1. customThe reaction was purged with N2
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-ee9ef3c91fbb407f810524f0c6646fc2
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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