Diisopropylethylamine → HCID 118318871, compound

HRID 921222Notes

Reaction equation

HRID 921222 reaction equation
[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20]I)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].CCN(C(C)C)C(C)C.[CH2:44]([C:48]1[CH:58]=[C:57]([F:59])[CH:56]=[CH:55][C:49]=1[CH2:50][NH:51][CH:52]1[CH2:54][CH2:53]1)[CH2:45][CH:46]=[CH2:47]>C(#N)C>[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:51]([CH2:50][C:49]4[CH:55]=[CH:56][C:57]([F:59])=[CH:58][C:48]=4[CH2:44][CH2:45][CH:46]=[CH2:47])[CH:52]4[CH2:54][CH2:53]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 118307040HCID 118307040, compoundHCID 118318796(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318871HCID 118318871, compoundYield 73.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (53.3 mg, 0.091 mmol) in acetonitrile (2 mL) at 0° C. was added Hunig's Base (0.016 mL, 0.091 mmol) and N-(2-(but-3-en-1-yl)-4-fluorobenzyl)cyclopropanamine (20 mg, 0.091 mmol). It was stirred at 0° C. for 2 h and then quenched with water, extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by biotage, eluting with 20% EtOAc/hexane to obtain (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)-4-fluorobenzyl)(cyclopropyl)amino)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (45 mg, 0.067 mmol, 73.0% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ 7.36 (dd, J=8.3, 6.1 Hz, 1H), 6.89-6.78 (m, 2H), 6.41 (s, 1H), 6.06-5.95 (m, 2H), 5.80 (ddt, J=17.1, 10.3, 6.6 Hz, 1H), 5.41 (d, J=17.1 Hz, 1H), 5.17 (d, J=11.0 Hz, 1H), 5.03-4.92 (m, 2H), 4.30-4.13 (m, 2H), 4.01 (d, J=4.9 Hz, 2H), 3.88 (s, 2H), 3.80 (s, 2H), 2.76-2.69 (m, 2H), 2.63 (s, 3H), 2.33-2.22 (m, 2H), 2.10-1.87 (m, 4H), 1.72 (br. s., 1H), 1.36 (br. s., 3H), 1.27-1.21 (m, 12H), 0.48-0.31 (m, 4H), 4 protons from piperidine were missing. LCMS (M+1)=676.5.

Workup

  1. customquenched with water
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by biotage
  7. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-499cd209f44a4b7294ae946d1d907fe3
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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