Methyl iodide → HCID 86697448, compound
Reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:15][CH2:14][C@H:13]([NH:16][C:17](=O)OC(C)(C)C)[CH2:12]3)=[N:7][C:6]=12.IC.[H-].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:15][CH2:14][C@H:13]([NH:16][CH3:17])[CH2:12]3)=[N:7][C:6]=12Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
(S)-tert-butyl (1-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-3-yl)carbamate (3.6 g, 9.4 mmol) taken up in 15 mL DMF and cooled to 0° C. in an ice bath. Iodomethane (1.026 mL, 16.5 mmol) added and stirred 5 minutes. Then sodium hydride 60% in oil (754 mg, 18.8 mmol) was slowly added. Reaction stirred 5 minutes at 0° C. then removed from ice bath and stirred 30 minutes at room temperature. Reaction was quenched with ice then extracted with ethyl acetate 2×. Ethyl acetate fractions combined dried over magnesium sulfate filtered reduce in vacuo. This was then taken up in 26 mL DCM and 4 mL TFA added. Stirred 1 hour until complete by LC/MS. Reaction washed with 1N NaOH, DCM layer removed dried over magnesium sulfate filtered, reduced in vacuo to get 2.72 g crude product carried on as is to part C. LRMS (ESI) m/z 296/298 [(M+H)]+, calc'd for C11H14BrN5: 296.17.
Workup
- customReaction
- stirringstirred 5 minutes at 0° C.
- customthen removed from ice bath
- stirringstirred 30 minutes at room temperature
- customReaction
- customwas quenched with ice
- extractionthen extracted with ethyl acetate 2×
- dry with materialEthyl acetate fractions combined dried over magnesium sulfate
- filtrationfiltered
- addition4 mL TFA added
- stirringStirred 1 hour until complete by LC/MS
- customReaction
- washwashed with 1N NaOH, DCM layer
- customremoved
- dry with materialdried over magnesium sulfate
- filtrationfiltered
Sources & evidence
- ORD record
- ord-955087399fb243a9b79c4a7d0782014c
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09403832B2
Reaction notes
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