Trimethylsilylacetylene → N-Cyclobutyl-6-(2-(trimethylsilyl)ethynyl)pyridazin-3-amine

HRID 706798Notes

Reaction equation

Br[C:2]1[N:7]=[N:6][C:5]([NH:8][CH:9]2[CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15].C(N(CC)C(C)C)(C)C>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.CN(C=O)C>[CH:9]1([NH:8][C:5]2[N:6]=[N:7][C:2]([C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13])=[CH:3][CH:4]=2)[CH2:12][CH2:11][CH2:10]1

Participants

Conditions

Temperature: 80 °C

Procedure

6-Bromo-N-cyclobutylpyridazin-3-amine (0.60 g, 2.63 mmol), trimethylsilylacetylene (TMSA) (1.29 g, 13.1 mmol), Pd(PPh3)4 (0.15 g), and CuI (0.04 mg) were placed in a vial with a rubber septum. After the mixture underwent 3 cycles of vacuum/filling with Ar2, DMF (3.0 mL) and N,N-diisopropylethylamine (DIPEA) (0.41 g, 3.2 mmol) were added. The mixture was then stirred at 80° C. for 16 hrs. The reaction mixture was concentrated and the resulting residue was purified by silica gel chromatography (eluent: 30% ethyl acetate in n-hexane, ethyl acetate was added 0.5% Et3N) to give an off-white solid (0.48 g, 74.5%). 1H NMR (300 MHz, CDCl3) δ: 7.26-7.29 (1 H, d, J=9.0 Hz), 6.50-6.53 (1 H, d, J=9.0 Hz), 5.55 (1 H, s), 4.17-4.24 (1 H, m), 2.40-2.46 (2 H, m), 1.89-1.98 (2 H, m), 1.77-1.85 (2 H, m), 0.28 (9 H, s).

Workup

concentrationThe reaction mixture was concentrated
customthe resulting residue was purified by silica gel chromatography (eluent: 30% ethyl acetate in n-hexane, ethyl acetate was added 0.5% Et3N)

Sources & evidence

ORD record: ord-da23914f767f486bb5cc879997cc42cc
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174996B2

Reaction notes

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