2-Methoxyethyl chloroformate → 2-Methoxyethyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

HRID 1844354Notes

Reaction equation

HRID 1844354 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[N:7][C:6]=12.[C:17](Cl)(=[O:23])[O:18][CH2:19][CH2:20][O:21][CH3:22]>CCOC(C)=O>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:18][CH2:19][CH2:20][O:21][CH3:22])=[O:23])[CH2:13][CH2:12]3)=[N:7][C:6]=12

Participants

4

Reactant 2

HCID 694002-Methoxyethyl chloroformateHCID 866974343-Bromo-5-(piperazin-1-yl)pyrazolo[1,5-a]pyrimidine

Product 1

HCID 866974402-Methoxyethyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To 10.00 g (35.44 mmol) of 3-bromo-5-(piperazin-1-yl)pyrazolo[1,5-a]pyrimidine dissolved in 120 mL of EtOAc, at 0° C. was added 5.40 g (38.99 mmol) of 2-methoxyethyl carbonochloridate, followed by 9.86 mL (70.88 mmol) of TEA. After 5 minutes, the ice bath was removed, and the reaction mixture stirred at RT. After 5 hr, LCMS showed that the reaction was complete. It was diluted with EtOAc, quenched with brine, and the organic layer dried over MgSO4. It was concentrated and purified on the ISCO with a 330 g column eluting with 0-9% MeOH/DCM to obtain the desired product, 12.63 g (93%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.42 (s, 3 H) 3.62-3.69 (m, 6 H) 3.73-3.82 (m, 4 H) 4.26-4.35 (m, 2 H) 6.36 (d, J=7.83 Hz, 1 H) 7.86 (s, 1 H) 8.27 (d, J=7.83 Hz, 1 H). LRMS (ESI) m/e 384 [(M+H)+, (doublet), calcd for C14H15BrN5O3 383].

Workup

  1. customthe ice bath was removed
  2. waitAfter 5 hr
  3. additionIt was diluted with EtOAc
  4. customquenched with brine
  5. dry with materialthe organic layer dried over MgSO4
  6. concentrationIt was concentrated
  7. custompurified on the ISCO with a 330 g column
  8. washeluting with 0-9% MeOH/DCM

Sources & evidence

ORD record
ord-84fc7b520ef9448c8a7c38afd6696c43
Source dataset
uspto-grants-2015_02
Patent number
US08946415B2

Reaction notes

Loading…