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

HRID 1049143Notes

Reaction equation

HRID 1049143 reaction equation
Cl.[CH3:2][C:3]1[C:7]([B:8]2[O:12][C:11]([CH3:14])([CH3:13])[C:10]([CH3:16])([CH3:15])[O:9]2)=[CH:6][N:5]([C:17]2([CH2:21][C:22]#[N:23])[CH2:20][NH:19][CH2:18]2)[N:4]=1.Cl[C:25]1[N:26]=[CH:27][C:28]([C:31]([NH:33][CH:34]([CH3:36])[CH3:35])=[O:32])=[N:29][CH:30]=1.C(N(CC)C(C)C)(C)C.C(O)(C)(C)C>>[C:22]([CH2:21][C:17]1([N:5]2[CH:6]=[C:7]([B:8]3[O:9][C:10]([CH3:16])([CH3:15])[C:11]([CH3:13])([CH3:14])[O:12]3)[C:3]([CH3:2])=[N:4]2)[CH2:18][N:19]([C:25]2[N:26]=[CH:27][C:28]([C:31]([NH:33][CH:34]([CH3:36])[CH3:35])=[O:32])=[N:29][CH:30]=2)[CH2:20]1)#[N:23]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 1038030435-chloro-N-(propan-2-yl)pyrazine-2-carboxamideHCID 131736002{3-[3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile HCl salt

Product 1

HCID 1317360015-{3-(Cyanomethyl)-3-[3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylpyrazine-2-carboxamide

Conditions

Temperature
100 °C

Procedure

A mixture of {3-[3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile HCl salt (0.43 g, 1.3 mmol), 5-chloro-N-isopropylpyrazine-2-carboxamide (0.24 g, 1.2 mmol) and N,N-diisopropylethylamine (0.63 mL, 3.6 mmol) in tert-butyl alcohol (12 mL, 120 mmol) was heated at 100° C. for 4 h. After cooling, the solvent was removed under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-60%) to afford the desired product. LCMS cacld. for C23H33BN7O3 (M+1)+: m/z=466.3. Found: 466.2.

Workup

  1. temperatureAfter cooling
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was purified by flash chromatography on a silica gel column
  4. washeluting with ethyl acetate in hexanes (0-60%)

Sources & evidence

ORD record
ord-4b6aade5ef394412b2b4d2f2bca15ca7
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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