Sodium hydride → HCID 118318867, compound

HRID 921215Notes

Reaction equation

HRID 921215 reaction equation
[CH2:1]([C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[CH2:12][OH:13])[CH2:2][CH:3]=[CH2:4].[CH2:14]([O:17][C:18]1([CH3:47])[CH2:23][CH2:22][N:21]([C:24]2[N:29]3[N:30]=[C:31]([CH2:33]I)[CH:32]=[C:28]3[N:27]=[C:26]([CH3:35])[C:25]=2[C@H:36]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:20][CH2:19]1)[CH:15]=[CH2:16].[H-].[Na+]>CN(C=O)C>[CH2:14]([O:17][C:18]1([CH3:47])[CH2:19][CH2:20][N:21]([C:24]2[N:29]3[N:30]=[C:31]([CH2:33][O:13][CH2:12][C:6]4[CH:7]=[CH:8][C:9]([F:11])=[CH:10][C:5]=4[CH2:1][CH2:2][CH:3]=[CH2:4])[CH:32]=[C:28]3[N:27]=[C:26]([CH3:35])[C:25]=2[C@H:36]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:22][CH2:23]1)[CH:15]=[CH2:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118307025HCID 118307025, 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 118318867HCID 118318867, compoundYield 32.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (2-(but-3-en-1-yl)-4-fluorophenyl)methanol (43.8 mg, 0.243 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 (142 mg, 0.243 mmol) in DMF (5 mL) at 0° C. was added NaH (9.72 mg, 0.243 mmol) and the reaction was stirred at 0° C. for 3 h. It was then quenched with water, 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 20% EtOAc/hexane to isolate (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)-4-fluorobenzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.079 mmol, 32.3% yield) as an oil. LCMS (M+1)=637.3.

Workup

  1. customIt was then quenched with water
  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 20% EtOAc/hexane

Sources & evidence

ORD record
ord-1b9e9a21913f4f8ea0c46d3e155e9e07
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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