Ethyl Acetate → Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate

HRID 1396812Notes

Reaction equation

HRID 1396812 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][CH:27]=[C:4]2[N:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH2:42][CH:41]3[N:43]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH:38]([CH2:39][CH2:40]3)[CH:37]=2)O1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[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][CH:27]=[C:4]2[N:3]=[C:2]([C:36]2[CH2:37][CH:38]3[N:43]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH:41]([CH2:40][CH2:39]3)[CH:42]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 53393373Tert-butyl 3-(tetramethyl-1,3,2-dioxaborolan-2-yl)-8-azabicyclo(3.2.1)oct-2-ene-8-carboxylateHCID 772312195-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 66584641Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To 5-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (11.1 g, 25.8 mmol) in DME (200 mL) was added tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate (9.5 g, 28.4 mmol), PdCl2(dppf)2 (2.1 g, 2.6 mmol) and 2M Na2CO3 (100 ml). The reaction was heated at 100° C. for 16 hours, at which time LC/MS analysis confirmed full consumption of starting material. On cooling, H2O (80 ml) and EtOAc (200 ml) were added and the organics were extracted with EtOAc (2×250 ml), dried (Na2SO4) and concentrated in vacuo to give a crude product. Gradient column chromatography on silica eluting with 10% to 60% EtOAc/hexanes(0-50%) gave tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate.

Workup

  1. customconsumption of starting material
  2. temperatureOn cooling
  3. additionH2O (80 ml) and EtOAc (200 ml) were added
  4. extractionthe organics were extracted with EtOAc (2×250 ml)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto give a crude product

Sources & evidence

ORD record
ord-2522206ea5274dec80c3962194bf186e
Source dataset
uspto-grants-2014_12
Patent number
US08901142B2

Reaction notes

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