Sodium hydride → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((4-fluoro-2-vinylbenzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921246Notes

Reaction equation

HRID 921246 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[C:4]([CH:10]=[CH2:11])[CH:3]=1.[CH2:12]([O:15][C:16]1([CH3:45])[CH2:21][CH2:20][N:19]([C:22]2[N:27]3[N:28]=[C:29]([CH2:31]I)[CH:30]=[C:26]3[N:25]=[C:24]([CH3:33])[C:23]=2[C@H:34]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:18][CH2:17]1)[CH:13]=[CH2:14].[H-].[Na+]>CN(C=O)C>[CH2:12]([O:15][C:16]1([CH3:45])[CH2:17][CH2:18][N:19]([C:22]2[N:27]3[N:28]=[C:29]([CH2:31][O:9][CH2:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=4[CH:10]=[CH2:11])[CH:30]=[C:26]3[N:25]=[C:24]([CH3:33])[C:23]=2[C@H:34]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:20][CH2:21]1)[CH:13]=[CH2:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118307012(4-Fluoro-2-vinylphenyl)methanolHCID 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 118318886(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((4-fluoro-2-vinylbenzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 44.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (4-fluoro-2-vinylphenyl)methanol (39.1 mg, 0.257 mmol) in DMF (3 mL) at 0° C. was added (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (150 mg, 0.257 mmol) and NaH (10.26 mg, 0.257 mmol). It was then quenched with sat. NH4Cl, extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated to obtain an oil, which was then purified by biotage, eluting with 25% EtOAc/hexane to isolate (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((4-fluoro-2-vinylbenzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (70 mg, 0.115 mmol, 44.8% yield) as an oil. LCMS (M+1)=609.3.

Workup

  1. customIt was then quenched with sat. NH4Cl
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto obtain an oil, which
  7. customwas then purified by biotage
  8. washeluting with 25% EtOAc/hexane

Sources & evidence

ORD record
ord-4b4814167a764e008fe714a6c7b9ff4d
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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