cis-1-Ethoxy-2-(tri-n-butylstannyl)ethylene → 3-(6-phenylpyridin-3-yl)-5-(piperidin-4-yloxy)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

HRID 1913258Notes

Reaction equation

HRID 1913258 reaction equation
C[Si](C)(C)CCO[CH2:6][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]([O:29][CH:30]2[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]2)[C:9]=1Br.[CH2:54]([Sn](CCCC)(CCCC)/C=C\OCC)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>[C:23]1([C:20]2[N:19]=[CH:18][C:17]([C:16]3[CH:15]=[N:14][N:13]4[C:8]5[NH:7][CH:6]=[CH:54][C:9]=5[C:10]([O:29][CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)=[N:11][C:12]=34)=[CH:22][CH:21]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 2

HCID 5706773cis-1-Ethoxy-2-(tri-n-butylstannyl)ethyleneHCID 66733399Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yloxy)piperidine-1-carboxylate

Product 1

HCID 1363324193-(6-phenylpyridin-3-yl)-5-(piperidin-4-yloxy)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

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-yloxy)piperidine-1-carboxylate (Int-11c, 0.26 mmol, 216 mg), Pd(PPh3)4 (30 mg, 0.026 mmoL), (Z)-tributyl(2-ethoxyvinyl)stannane (142 mg, 0.39 mmoL) in Dioxane (6 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 (Z)-ethyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(2-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexyl)acetate (Int-11d) was treated with 50% TFA in H2O (6 mL) and stirred overnight. The reaction mixture was concentrated in vacuo. Purification with prep-LC provided 3-(6-phenylpyridin-3-yl)-5-(piperidin-4-yloxy)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine (Int-11e): LCMS tR=2.71 Min (10 min run, UV254nm). Mass calculated for, M+410.1, observed m/z 411.1 (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 (Z)-ethyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(2-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexyl)acetate (Int-11d) was treated with 50% TFA in H2O (6 mL)
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customPurification

Sources & evidence

ORD record
ord-55f67737f0e44c1aa4cc650e8fdfe8a0
Source dataset
uspto-grants-2013_12
Patent number
US08609675B2

Reaction notes

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