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

HRID 921083Notes

Reaction equation

HRID 921083 reaction equation
[CH2:1]([O:4][C:5]1([CH3:45])[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]=[C:28]([OH:32])[CH:27]=5)[N:23]=[N:22]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:33])[C:12]=2[C@H:34]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].C([O-])([O-])=O.[K+].[K+].[CH2:52](Br)[CH:53]=[CH2:54]>CN(C=O)C>[CH2:1]([O:4][C:5]1([CH3:45])[CH2:6][CH2:7][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]=[C:28]([O:32][CH2:54][CH:53]=[CH2:52])[CH:27]=5)[N:23]=[N:22]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:33])[C:12]=2[C@H:34]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:9][CH2:10]1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 118318750(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318752(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-(allyloxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 32.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0525 g, 0.085 mmol), K2CO3 (0.047 g, 0.340 mmol) and allyl bromide (0.074 ml, 0.850 mmol) in DMF (3 mL) was heated at 60° C. for 24 h. Then, cooled and purified prep-HPLC to afford (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-(allyloxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0184 g, 0.028 mmol, 32.9% yield) as colorless paste. 1H NMR (500 MHz, CDCl3) δ 7.90 (s, 1H), 7.46 (dd, J=1.5, 2.4 Hz, 1H), 7.35-7.38 (m, 1H), 7.29-7.34 (m, 1H), 6.90 (ddd, J=1.0, 2.6, 8.1 Hz, 1H), 6.51 (s, 1H), 5.98-6.14 (m, 2H), 5.88 (br. s., 1H), 5.79 (s, 2H), 5.45 (qd, J=1.6, 17.2 Hz, 2H), 5.31 (qd, J=1.4, 10.4 Hz, 1H), 5.20 (qd, J=1.6, 10.4 Hz, 1H), 4.62 (td, J=1.5, 5.3 Hz, 2H), 4.14-4.28 (m, 2H), 4.00 (d, J=5.0 Hz, 2H), 2.70-3.90 (m, 3H), 2.61 (s, 3H), 1.85-2.03 (m, 3H), 1.64-1.74 (m, 2H), 1.31 (s, 3H), 1.25 (t, J=7.1 Hz, 3H), 1.24 (s, 9H). LCMS (M+H)=658.6.

Workup

  1. temperatureThen, cooled
  2. custompurified prep-HPLC

Sources & evidence

ORD record
ord-a65ccf6859164e44b373a6c4194b6bc8
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

Loading…