Tetrabutylammonium Fluoride → 4-(6-Ethynyl-3-methylindazol-1-yl)pyrimidin-2-amine

HRID 1398554Notes

Reaction equation

HRID 1398554 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]#[C:12][Si](C)(C)C)=[CH:8][CH:9]=2)[N:4]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[N:18]=2)[N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:11]([C:7]1[CH:6]=[C:5]2[C:10]([C:2]([CH3:1])=[N:3][N:4]2[C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[N:18]=2)=[CH:9][CH:8]=1)#[CH:12]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 681819134-{3-Methyl-6-[2-(trimethylsilyl)ethynyl]indazol-1-yl}pyrimidin-2-amine

Product 1

HCID 866695904-(6-Ethynyl-3-methylindazol-1-yl)pyrimidin-2-amineYield 64.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-{3-methyl-6-[2-(trimethylsilyl)ethynyl]indazol-1-yl}pyrimidin-2-amine (600 mg, 1.87 mmol) in THF (15 ml) was added TBAF (2.24 mL of a 1M solution in THF, 2.24 mmol) and the reaction mixture was allowed to stand for 0.5 hr. The reaction mixture was concentrated in vacuo, DCM (5 ml) was added and the concentration repeated (×2). The crude product was purified by flash chromatography (Biotage, 3-10% methanol in DCM) to give the title intermediate as a yellow solid (300 mg): 1H NMR (500 MHz, DMSO) delta 2.58 (3H, s), 4.37 (1H, s), 7.14-6.86 (3H, m), 7.40 (1H, dd, J=8.2, 1.1 Hz), 7.85 (1H, d, J=8.2 Hz), 8.26 (1H, d, J=5.5 Hz), 8.98 (1H, s); LC-MS: m/z=+250.35 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo, DCM (5 ml)
  2. additionwas added
  3. concentrationthe concentration
  4. customThe crude product was purified by flash chromatography (Biotage, 3-10% methanol in DCM)

Sources & evidence

ORD record
ord-8544725e239b47b8b414d5398a9ef202
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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