Sodium hydride → HCID 131734923, compound

HRID 921195Notes

Reaction equation

HRID 921195 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:10])[CH3:9])=[C:4]([O:11][C@H:12]([CH2:14][CH:15]=[CH2:16])[CH3:13])[CH:3]=1.[CH2:17]([O:20][C:21]1([CH3:50])[CH2:26][CH2:25][N:24]([C:27]2[N:32]3[N:33]=[C:34]([CH2:36]I)[CH:35]=[C:31]3[N:30]=[C:29]([CH3:38])[C:28]=2[C@H:39]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:23][CH2:22]1)[CH:18]=[CH2:19].[H-].[Na+]>CN(C=O)C>[CH2:17]([O:20][C:21]1([CH3:50])[CH2:22][CH2:23][N:24]([C:27]2[N:32]3[N:33]=[C:34]([CH2:36][O:10][CH:8]([C:5]4[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][C:4]=4[O:11][C@H:12]([CH2:14][CH:15]=[CH2:16])[CH3:13])[CH3:9])[CH:35]=[C:31]3[N:30]=[C:29]([CH3:38])[C:28]=2[C@H:39]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:25][CH2:26]1)[CH:18]=[CH2:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118307079HCID 118307079, 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 131734923HCID 131734923, compoundYield 17.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1-(4-methyl-2-((S)-pent-4-en-2-yloxy)phenyl)ethanol (41.5 mg, 0.188 mmol) and (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (100 mg, 0.171 mmol) in DMF (5 mL) was added sodium hydride (7.53 mg, 0.188 mmol) at 0° C. It was then stirred at 0° C. for 4 h and then quenched with NH4Cl, extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. The residue was then purified by biotage, eluting with 25% EtOAc/hexane to isolate (2S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-((1-(4-methyl-2-((S)-pent-4-en-2-yloxy)phenyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (20 mg, 0.030 mmol, 17.27% yield) as an oil. LCMS (M+1)=677.5.

Workup

  1. customquenched with NH4Cl
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was then purified by biotage
  7. washeluting with 25% EtOAc/hexane

Sources & evidence

ORD record
ord-fdecd32569c94d6e8c06647d3b6ca31d
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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