Sodium Iodide → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921112Notes

Reaction equation

HRID 921112 reaction equation
[CH2:1]([O:4][C:5]1([CH3:38])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20]OS(C)(=O)=O)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:26])[C:12]=2[C@H:27]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[I-:39].[Na+]>CC(C)=O.CCOC(C)=O>[CH2:1]([O:4][C:5]1([CH3:38])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][I:39])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:26])[C:12]=2[C@H:27]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 5238Sodium IodideHCID 118318795(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((methylsulfonyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318796(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 84.1%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((methylsulfonyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.62 g, 1.122 mmol) in acetone (6 ml) was added sodium iodide (0.673 g, 4.49 mmol) and the mixture was stirred at rt for 45 min. The reaction was diluted with EtOAc and washed with water. The organic phase was dried (Na2SO4), filtered and concentrated. The crude oil was purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane; 20 CV) to give (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.5519 g, 0.944 mmol, 84% yield) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.53 (s, 1H), 6.16-5.99 (m, 1H), 5.99-5.77 (m, 1H), 5.64-5.39 (m, 1H), 5.32-5.14 (m, 1H), 4.56 (s, 2H), 4.35-4.17 (m, 2H), 4.03 (d, J=4.9 Hz, 2H), 2.59 (s, 3H), 1.93 (br. s., 4H), 1.36 (s, 3H), 1.31-1.18 (m, 12H). 4 piperidine protons not seen. LCMS (M+H) calcd for C25H38IN4O4: 585.19. found: 585.5.

Workup

  1. washwashed with water
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude oil was purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane; 20 CV)

Sources & evidence

ORD record
ord-7dccc93e563746b3b29394e83f1ecab3
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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