Stannane, tributyl(1-ethoxyethenyl)- → 1-(7-Amino-3-(6-phenylpyridin-3-yl)-5-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)ethanone

HRID 1913252Notes

Reaction equation

HRID 1913252 reaction equation
C[Si](C)(C)CCOC[N:7](COCC[Si](C)(C)C)[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[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]2)[C:9]=1Br.C([Sn](CCCC)(CCCC)[C:58]([O:60]CC)=[CH2:59])CCC>O1CCOCC1.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>[NH2:7][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[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[C:9]=1[C:58](=[O:60])[CH3:59]

Participants

5

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 66584941Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate

Product 1

HCID 667379881-(7-Amino-3-(6-phenylpyridin-3-yl)-5-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)ethanone

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A degassed mixture of tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (Int-91,154 mg, 0.19 mmoL), Pd(PPh3)4 (22 mg, 0.019 mmoL), tributyl(1-ethoxyvinyl)stannane (103 mg, 0.28 mmoL) in dioxane (3 mL) was heated at 100° C. overnight. The reaction mixture was cooled to room temperature, filtered through 9:1 SiO2:KF plug and concentrated in vacuo. The crude tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (Int-9j) was treated with 50% TEA in H2O (4 mL) until the disappearance of starting material in LCMS. Concentration afforded crude 1-(7-amino-3-(6-phenylpyridin-3-yl)-5-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)ethanone (Int-9k), which was then heated under microwave conditions with N2H4.H2O (800 uL) and NMP (6 mL) first at 100° C. for 30 min and then at 200° C. for 1 h. Purification with prep-LC provided 3-methyl-6-(6-phenylpyridin-3-yl)-4-(piperidin-4-yl)-1H-dipyrazolo[1,5-a:4′,3′-e]pyrimidine (Int-91): LCMS tR=2.49 Min (10 min run, UV254m). Mass calculated for, M+409.2, observed LC/MS m/z 410.6 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through 9:1 SiO2
  3. concentrationKF plug and concentrated in vacuo
  4. additionThe crude tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (Int-9j) was treated with 50% TEA in H2O (4 mL) until the disappearance of starting material in LCMS
  5. concentrationConcentration

Sources & evidence

ORD record
ord-da0f754e8ad04925856f564e1d8a30de
Source dataset
uspto-grants-2013_12
Patent number
US08609675B2

Reaction notes

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