2-(Tributylstannyl)pyridine → Tert-butyl 3-(3-(2,2'-bipyridin-5-yl)-7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 2368974Notes

Reaction equation

HRID 2368974 reaction equation
[CH3:1][Si:2]([CH3:48])([CH3:47])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20](Cl)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:24]2[CH2:30][CH:29]3[N:31]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:26]([CH2:27][CH2:28]3)[CH2:25]2)[CH:9]=1.C([Sn](CCCC)(CCCC)[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=1)CCC>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.CC#N>[N:19]1[CH:18]=[C:17]([C:16]2[CH:15]=[N:14][N:13]3[C:8]([N:7]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:48])([CH3:47])[CH3:1])=[CH:9][C:10]([CH:24]4[CH2:30][CH:29]5[N:31]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:26]([CH2:27][CH2:28]5)[CH2:25]4)=[N:11][C:12]=23)[CH:22]=[CH:21][C:20]=1[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=1

Participants

5

Reactant 2

HCID 6077842-(Tributylstannyl)pyridineHCID 86674906Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 86686734Tert-butyl 3-(3-(2,2'-bipyridin-5-yl)-7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

To tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (Int-2a) (2.66 mmol, 1904 mg) and Pd(PPh3)4 (0.27 mmol, 307 mg) in a 20 mL microwave vial was added 2-(Tributylstannyl)pyridine (5.25 mmol, 1.7 mL) and CH3CN (12 mL). The reaction was run in the microwave at 150° C. for 45 mins. The reaction was filtered through a pad of KF (˜7 g) and SiO2 (˜7 g) with the aid of EtOAc and fractions containing product were combined and concentrated to give a brown oil. Gradient column chromatography on silica (80 g) eluting with 5%-40% EtOAc/hexanes gave tert-butyl 3-(3-(2,2′-bipyridin-5-yl)-7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate, LCMS tR=2.1 Min (5 min run, UV254nm). Mass calculated for, M+H 758.4, observed LC/MS m/z 758.3 (M+H).

Workup

  1. filtrationThe reaction was filtered through a pad of KF (˜7 g) and SiO2 (˜7 g) with the aid of EtOAc and fractions
  2. additioncontaining product
  3. concentrationconcentrated
  4. customto give a brown oil
  5. washGradient column chromatography on silica (80 g) eluting with 5%-40% EtOAc/hexanes

Sources & evidence

ORD record
ord-28d2352d2cd64ffc9ffdc9388620d033
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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