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-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrazine-2-carboxamide

HRID 1049127Notes

Reaction equation

Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][C@@H:11]([CH3:16])[C:12]([F:15])([F:14])[F:13])=[O:9])=[N:6][CH:7]=1.Cl.[CH3:18][C:19]1([CH3:38])[C:23]([CH3:25])([CH3:24])[O:22][B:21]([C:26]2[CH:27]=[N:28][N:29]([C:31]3([CH2:35][C:36]#[N:37])[CH2:34][NH:33][CH2:32]3)[CH:30]=2)[O:20]1.C(N(CC)C(C)C)(C)C>O1CCOCC1>[C:36]([CH2:35][C:31]1([N:29]2[CH:30]=[C:26]([B:21]3[O:22][C:23]([CH3:25])([CH3:24])[C:19]([CH3:38])([CH3:18])[O:20]3)[CH:27]=[N:28]2)[CH2:34][N:33]([C:2]2[N:3]=[CH:4][C:5]([C:8]([NH:10][C@@H:11]([CH3:16])[C:12]([F:15])([F:14])[F:13])=[O:9])=[N:6][CH:7]=2)[CH2:32]1)#[N:37]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 5-chloro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrazine-2-carboxamide (254 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) 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 (0.49 g, 97%). LCMS cacld. for C22H28BF3N7O3 (M+1)+: m/z=506.2. Found: 506.1.

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-d07cb83753ae4568b75f6129350a1b63
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382231B2

Reaction notes

Loading…