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

HRID 921077Notes

Reaction equation

HRID 921077 reaction equation
[CH2:1]([O:4][C:5]1([CH3:40])[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]([CH2:26][OH:27])[N:23]=[N:22]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:28])[C:12]=2[C@H:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[H-].[Na+].[CH2:43](Br)[CH:44]=[CH2:45]>CN(C=O)C>[CH2:1]([O:4][C:5]1([CH3:40])[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]([CH2:26][O:27][CH2:45][CH:44]=[CH2:43])[N:23]=[N:22]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:28])[C:12]=2[C@H:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 131734900(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318737(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-((allyloxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 57.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred colorless solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate in DMF (2 mL) was added at once 60% NaH (10 mg, 0.250 mmol) at 0° C. After 5 min, allyl bromide (0.085 ml, 0.981 mmol) was added to the brown reaction mixture and stirred for 30 min at 0° C. and 1 h at rt. Then, quenched with EtOH and purified by prep-HPLC to give (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-((allyloxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0334 g, 0.056 mmol, 57.2% yield) as brown paste. 1H NMR (500 MHz, CDCl3) δ 7.67 (s, 1H), 6.45 (s, 1H), 5.98-6.08 (m, 1H), 5.83-5.97 (m, 2H), 5.73 (s, 2H), 5.40-5.53 (m, 1H), 5.30 (qd, J=1.6, 17.2 Hz, 1H), 5.17-5.24 (m, 2H), 4.64 (d, J=0.5 Hz, 2H), 4.13-4.28 (m, 2H), 4.06 (td, J=1.4, 5.7 Hz, 2H), 4.00-4.03 (m, 2H), 2.60 (s, 3H), 1.87-2.03 (m, 3H), 1.64-1.75 (m, 1H), 1.34 (s, 3H), 1.20-1.26 (m, 12H). LCMS (M+H)=596.6.

Workup

  1. customThen, quenched with EtOH
  2. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-0ce5234fce614a2eacf7a1810bd12ad8
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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