Diisopropylethylamine → Methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 1400769Notes

Reaction equation

HRID 1400769 reaction equation
[Br:1][C:2]1[CH:17]=[C:5]2[N:6]=[C:7]([CH3:16])[C:8]([CH2:11][C:12]([O:14][CH3:15])=[O:13])=[C:9](Cl)[N:4]2[N:3]=1.CC1(C)C(C)(C)OB(C2C=C(C)C=CC=2OC(C(C)C=C)C)O1.BrC1C=C(N)NN=1.[CH2:48]([O:51][C:52]1([CH3:58])[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)[CH:49]=[CH2:50].CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH2:48]([O:51][C:52]1([CH3:58])[CH2:53][CH2:54][N:55]([C:9]2[N:4]3[N:3]=[C:2]([Br:1])[CH:17]=[C:5]3[N:6]=[C:7]([CH3:16])[C:8]=2[CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:56][CH2:57]1)[CH:49]=[CH2:50]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 86670270Methyl 2-(2-bromo-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateHCID 867107774-(Allyloxy)-4-methylpiperidineHCID 867108164,4,5,5-Tetramethyl-2-(5-methyl-2-((3-methylpent-4-en-2-yl)oxy)phenyl)-1,3,2-dioxaborolaneHCID 178507227HCID 178507227, compound

Product 1

HCID 86710822Methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 2-(2-bromo-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (prepared according to the procedure for intermediate 4 starting from 3-bromo-1H-pyrazol-5-amine; 13.4 g, 41.9 mmol, 1 equiv), 4-(allyloxy)-4-methylpiperidine (7.16 g, 46.1 mmol, 1.1 equiv), and DIEA (17.6 mL, 101 mmol, 2.4 equiv) in DMF (84 mL) was heated at 60° C. for 2 h. The reaction was then added to water and extracted with ether (×2). Combined ether extracts dried (MgSO4) and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (0-50% EtOAc/hex) to provide methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (17.7 g, 97%). 1H NMR (500 MHz, CDCl3) δ 6.52 (s, 1H), 6.02 (ddt, J=17.2, 10.4, 5.2 Hz, 1H), 5.43 (dd, J=17.2, 1.6 Hz, 1H), 5.22 (dq, J=10.4, 1.5 Hz, 1H), 3.99 (dt, J=5.2, 1.6 Hz, 2H), 3.77 (s, 3H), 3.79-3.76 (m, 2H), 3.70-3.56 (m, J=7.4 Hz, 2H), 3.33 (br. s., 2H), 2.50 (s, 3H), 1.97-1.89 (m, 2H), 1.87-1.78 (m, J=9.3 Hz, 2H), 1.32 (s, 3H). LCMS (M+1)=437.20.

Workup

  1. extractionextracted with ether (×2)
  2. dry with materialCombined ether extracts dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by silica gel flash chromatography (0-50% EtOAc/hex)

Sources & evidence

ORD record
ord-f31c6f3641e240b8806bc5a801046388
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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