Methanesulfonyl chloride → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((methylsulfonyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921111Notes

Reaction equation

HRID 921111 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][OH:21])[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][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[CH3:35][S:36](Cl)(=[O:38])=[O:37]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[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:21][S:36]([CH3:35])(=[O:38])=[O:37])[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][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 118318735(S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318795(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((methylsulfonyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 106.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.50 g, 1.054 mmol) in DCM (6 ml) cooled to 0° C. were added DMAP (0.013 g, 0.105 mmol) and TEA (0.294 ml, 2.107 mmol) followed by methanesulfonyl chloride (0.098 ml, 1.264 mmol) and the resulting solution was stirred at 0° C. After 45 min, the reaction was diluted with DCM and quenched with sat'd aq NaHCO3. The organic phase was washed with water, dried and concentrated to give (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((methylsulfonyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.62 g, 1.122 mmol, 106% yield) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.63 (s, 1H), 6.15-5.97 (m, 1H), 5.98-5.81 (m, 1H), 5.55-5.38 (m, 3H), 5.29-5.20 (m, 1H), 4.32-4.11 (m, 2H), 4.02 (d, J=4.9 Hz, 2H), 3.06 (s, 3H), 2.63 (s, 3H), 1.93 (br. s., 4H), 1.35 (s, 3H), 1.29-1.19 (m, 12H).

Workup

  1. customquenched with sat'd aq NaHCO3
  2. washThe organic phase was washed with water
  3. customdried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-7331172d797b41f6af844edecbbb1673
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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