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

HRID 921204Notes

Reaction equation

HRID 921204 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][OH:12])[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:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=4[CH2:1][CH2:2][CH:3]=[CH2:4])[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 12063831(2-(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 118318858(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (2-(but-3-en-1-yl)phenyl)methanol (35.1 mg, 0.216 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 (115 mg, 0.197 mmol) and NaH (7.87 mg, 0.197 mmol). It was then stirred at 0° C. for 4 h. The reaction mixture was 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)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (55 mg, 0.089 mmol, 45.2% yield) as an oil. LCMS (M+1)=619.4.

Workup

  1. customThe reaction mixture was quenched 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-35568d694c6e46448e99989c8b33da80
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

Loading…