Sodium Bicarbonate → Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

HRID 589193Notes

Reaction equation

HRID 589193 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][C:27]([C:28]3[CH:29]=[N:30][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][CH:33]=3)=[C:4]2[N:3]=1.[CH:40]12[N:47]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH:44]([CH2:45][CH2:46]1)[CH2:43][NH:42][CH2:41]2.C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.O>[CH3:14][Si:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][O:10][CH2:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]1[N:5]2[N:25]=[CH:26][C:27]([C:28]3[CH:29]=[N:30][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][CH:33]=3)=[C:4]2[N:3]=[C:2]([N:42]2[CH2:41][CH:40]3[N:47]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH:44]([CH2:45][CH2:46]3)[CH2:43]2)[CH:7]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 157409088-Boc-3,8-diaza-bicyclo(3.2.1)octaneHCID 866647885-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 67295265Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 5-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (226 mg, 0.39 mmol), tert-butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate (330 mg, 1.56 mmol), NaHCO3 (196 mg, 2.33 mmol) in NMP (4 mL) was heated at 130° C. overnight. The mixture was cooled to room temperature and diluted with H2O and then extracted with ethyl acetate (×2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation of solvent afforded the crude displacement compound. Purification by column chromatography afforded tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate: LCMS tR=3.38 Min (5 min run, UV254nm). Mass calculated for, M+H 758.4, observed m/z 758.3 (M+H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (×2)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with Na2SO4
  5. customEvaporation of solvent
  6. customafforded the crude displacement compound
  7. customPurification by column chromatography

Sources & evidence

ORD record
ord-0a655c4fb8a24dcc8ddf6f2b0f8e21fa
Source dataset
uspto-grants-2016_01
Patent number
US09227971B2

Reaction notes

Loading…