1,4-Dioxane → Tert-butyl 7-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate

HRID 2369003Notes

Reaction equation

HRID 2369003 reaction equation
[CH3:1][Si:2]([CH3:55])([CH3:54])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[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]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:29]2[CH2:36][CH:35]3[N:37]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH:31]([CH2:32][O:33][CH2:34]3)[CH2:30]2)[C:9]=1Br.[CH2:56]([Sn](CCCC)(CCCC)[C:61]([O:63][CH2:64][CH3:65])=[CH2:62])[CH2:57][CH2:58][CH3:59].O1[CH2:79][CH2:78][O:77][CH2:76][CH2:75]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][Si:2]([CH3:55])([CH3:54])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[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]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:29]2[CH2:36][CH:35]3[N:37]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH:31]([CH2:32][O:33][CH2:34]3)[CH2:30]2)[C:9]=1[C:61]([O:63][CH2:64][CH3:65])=[CH2:62].[CH3:53][Si:50]([CH3:52])([CH3:51])[CH2:49][CH2:48][O:47][CH2:46][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:55])([CH3:54])[CH3:1])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:29]2[CH2:30][CH:31]3[N:37]([C:38]([O:40][CH2:56][CH2:57][CH2:58][CH3:59])=[O:39])[CH:35]([CH2:34][O:33][CH2:32]3)[CH2:36]2)[C:9]=1[C:78]([O:77][CH2:76][CH3:75])=[CH2:79]

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 66584563Tert-butyl 7-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate

Product 2

HCID 86686739Tert-butyl 7-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylateHCID 86686740Butyl 7-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

tert-butyl 7-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate (150 mg, 0.176 mmol) in dioxane (2 mL) was treated with Pd(PPh3)4 (20.3 mg, 0.0.176 mmol) and tributyl(1-ethoxyvinyl)tin (0.18 mL, 0.528 mmol) under argon and the mixture was heated at 100° C. for 16 h. Upon cooling, the mixture was filtered through a pad of 10% KF—SiO2 and the filtrate was evaporated off under reduced pressure to give a residue which was purified by column chromatography (SiO2, 0-40% hexane-EtOAc) to provide desired compound tort-butyl 7-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate. HPLC-MS tR=3.65 min (UV254 nm). Mass calculated for formula C45H66N6O6Si2 842.4; observed MH+ (LCMS) 843.2 (m/z).

Workup

  1. temperatureUpon cooling
  2. filtrationthe mixture was filtered through a pad of 10% KF—SiO2
  3. customthe filtrate was evaporated off under reduced pressure
  4. customto give a residue which
  5. customwas purified by column chromatography (SiO2, 0-40% hexane-EtOAc)

Sources & evidence

ORD record
ord-525e6dc184714581a275bb8db6cae80a
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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