Acetic Acid → Tert-butyl 3-{7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-6-bromo-3-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-5-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 589179Notes

Reaction equation

HRID 589179 reaction equation
[CH3:1][Si:2]([CH3:51])([CH3:50])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:23]([OH:26])([CH3:25])[CH3:24])=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:27]2[CH2:33][CH:32]3[N:34]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:29]([CH2:30][CH2:31]3)[CH2:28]2)[CH:9]=1.C(O)(=O)C.[Br:56]N1C(=O)CCC1=O.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(OCC)(=O)C>[CH3:49][Si:46]([CH3:47])([CH3:48])[CH2:45][CH2:44][O:43][CH2:42][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:1])([CH3:50])[CH3:51])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:23]([OH:26])([CH3:25])[CH3:24])=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:27]2[CH2:33][CH:32]3[N:34]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:29]([CH2:30][CH2:31]3)[CH2:28]2)[C:9]=1[Br:56]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 24477Sodium ThiosulfateHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 67299289Tert-butyl 3-{7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-3-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-5-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 68273121Tert-butyl 3-{7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-6-bromo-3-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-5-yl}-8-azabicyclo[3.2.1]octane-8-carboxylateYield 99.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

tert-butyl 3-{7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-3-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-5-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate (0.500 g, 0.676 mmol) was dissolved in acetic acid (3.5 mL, 62 mmol) and N-bromosuccinimide (144.2 mg, 0.8105 mmol) was added in a single portion, and the reaction was monitored by HPLC. The reaction was complete in less than 10 min and the mixture was diluted with ethyl acetate and poured into a 1:1 mixture of saturated aq. sodium bicarbonate and aq. sodium thiosulfate (20%). The layers were separated and the organics washed several times with sodium bicarbonate solution then brine. The organics were dried with magnesium sulfate, filtered and concentrated to provide 550 mg of the desired material.

Workup

  1. waitThe reaction was complete in less than 10 min
  2. customThe layers were separated
  3. dry with materialThe organics were dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5e5afffb148b42a183d4e96f4e147250
Source dataset
uspto-grants-2016_01
Patent number
US09227971B2

Reaction notes

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