Sodium hydride → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((3-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921210Notes

Reaction equation

HRID 921210 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]([CH2:11][OH:12])[CH:8]=[CH:9][CH:10]=1)[CH2:2][CH:3]=[CH2:4].[CH2:13]([O:16][C:17]1([CH3:46])[CH2:22][CH2:21][N:20]([C:23]2[N:28]3[N:29]=[C:30]([CH2:32]I)[CH:31]=[C:27]3[N:26]=[C:25]([CH3:34])[C:24]=2[C@H:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:19][CH2:18]1)[CH:14]=[CH2:15].[H-].[Na+]>CN(C=O)C>[CH2:13]([O:16][C:17]1([CH3:46])[CH2:18][CH2:19][N:20]([C:23]2[N:28]3[N:29]=[C:30]([CH2:32][O:12][CH2:11][C:7]4[CH:8]=[CH:9][CH:10]=[C:5]([CH2:1][CH2:2][CH:3]=[CH2:4])[CH:6]=4)[CH:31]=[C:27]3[N:26]=[C:25]([CH3:34])[C:24]=2[C@H:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:21][CH2:22]1)[CH:14]=[CH2:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68725274(3-(But-3-en-1-yl)phenyl)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 118318862(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((3-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 32.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (3-(but-3-en-1-yl)phenyl)methanol (40.2 mg, 0.248 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 (145 mg, 0.248 mmol) and NaH (9.92 mg, 0.248 mmol). The mixture was stirred at 0° C. for 3 h. It was then quenched with NH4Cl, 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-(((3-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.081 mmol, 32.6% yield) as an oil. LCMS (M+1)=619.5.

Workup

  1. customIt was then quenched with NH4Cl
  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-1bd32adb07bf455394bb51df9938bb94
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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