Sodium hydride → (S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2,4-difluoro-6-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid

HRID 921126Notes

Reaction equation

HRID 921126 reaction equation
[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20]I)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26]CC)=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[F:35][C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[C:38]([O:43][C@H:44]([CH2:46][CH:47]=[CH2:48])[CH3:45])[C:37]=1[CH2:49][OH:50].[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][O:50][CH2:49][C:37]4[C:38]([O:43][C@H:44]([CH2:46][CH:47]=[CH2:48])[CH3:45])=[CH:39][C:40]([F:42])=[CH:41][C:36]=4[F:35])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([OH:26])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 118307043(S)-(2,4-difluoro-6-(pent-4-en-2-yloxy)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 118307077(S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2,4-difluoro-6-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acidYield 13.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.2 g, 0.342 mmol) and (S)-(2,4-difluoro-6-(pent-4-en-2-yloxy)phenyl)methanol (0.094 g, 0.411 mmol) in DMF (1 mL) was added sodium hydride (0.021 g, 0.513 mmol) and the mixture was stirred at rt. After 4 h, the mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried (Na2SO4), filtered and concentrated and purified by Prep HPLC: to afford (S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2,4-difluoro-6-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid (0.030 g, 0.046 mmol, 13.35% yield) as a colorless oil. LCMS (M+H) calcd for C35H47F2N4O6: 657.34. found: 657.5.

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by Prep HPLC

Sources & evidence

ORD record
ord-b524b4f0ade145248d8599d5af41dcea
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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