Diisopropylethylamine → 5-{3-(Cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylpyrazine-2-carboxamide

HRID 1049130Notes

Reaction equation

Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][CH:11]([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=1.Cl.[CH3:15][C:16]1([CH3:35])[C:20]([CH3:22])([CH3:21])[O:19][B:18]([C:23]2[CH:24]=[N:25][N:26]([C:28]3([CH2:32][C:33]#[N:34])[CH2:31][NH:30][CH2:29]3)[CH:27]=2)[O:17]1.C(N(CC)C(C)C)(C)C>O1CCOCC1>[C:33]([CH2:32][C:28]1([N:26]2[CH:27]=[C:23]([B:18]3[O:19][C:20]([CH3:22])([CH3:21])[C:16]([CH3:35])([CH3:15])[O:17]3)[CH:24]=[N:25]2)[CH2:31][N:30]([C:2]2[N:3]=[CH:4][C:5]([C:8]([NH:10][CH:11]([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=2)[CH2:29]1)#[N:34]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 5-chloro-N-isopropylpyrazine-2-carboxamide (200 mg, 1.00 mmol), {3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile HCl salt (325 mg, 1.00 mmol, from Example 1, step 3) and N,N-diisopropylethylamine (401 μL, 2.30 mmol) in 1,4-dioxane (5.0 mL) was heated at 100° C. for 2 h. After cooling, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexane (gradient: 20-80%) to afford the desired product (0.26 g, 58%). LCMS cacld. for C22H31BN7O3 (M+1)+: m/z=452.3. Found: 452.2.

Workup

temperatureAfter cooling
concentrationthe mixture was concentrated under reduced pressure
customThe residue was purified by flash chromatography on a silica gel column
washeluting with ethyl acetate in hexane (gradient: 20-80%)

Sources & evidence

ORD record: ord-a0067b8931084fa68505f2693f23b75e
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382231B2

Reaction notes

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