Allyl bromide → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(2-((allyloxy)methyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921080Notes

Reaction equation

HRID 921080 reaction equation
[CH2:1]([O:4][C:5]1([CH3:46])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:21]4[CH:25]=[C:24]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[CH2:32][OH:33])[N:23]=[N:22]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]=2[C@H:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[H-].[Na+].[CH2:49](Br)[CH:50]=[CH2:51]>CN(C=O)C>[CH2:1]([O:4][C:5]1([CH3:46])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:21]4[CH:25]=[C:24]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[CH2:32][O:33][CH2:51][CH:50]=[CH2:49])[N:23]=[N:22]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]=2[C@H:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 118318749(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(2-(hydroxymethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318742(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(2-((allyloxy)methyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(2-(hydroxymethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.052 g, 0.082 mmol) in DMF (3 mL) was added 60% NaH (8.23 mg, 0.206 mmol) at 0° C. After 10 min allyl bromide (0.071 ml, 0.823 mmol) was added at once and stirred for 30 min at 0° C. and 1 h at rt. Then, quenched with EtOH, diluted with ether (50 mL), washed with water (3×5 mL), brine (5 mL), dried (MgSO4), filtered and concentrated to give (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(2-((allyloxy)methyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate as yellow paste which was used in the next step without purification. LCMS (M+H)=672.7.

Workup

  1. customThen, quenched with EtOH
  2. additiondiluted with ether (50 mL)
  3. washwashed with water (3×5 mL), brine (5 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8e8cec2c3576443bb6c0f1166b708ac2
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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