Stannane, tributyl(1-ethoxyethenyl)- → 2-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate

HRID 2368999Notes

Reaction equation

HRID 2368999 reaction equation
[CH3:1][Si:2]([CH3:56])([CH3:55])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][N:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:21]=3)=[C:12]2[N:11]=[C:10]([CH:28]2[CH2:33][CH2:32][C:31]([O:41][CH2:42][CH2:43][O:44][CH3:45])([C:34]([O:36][CH2:37][CH2:38][O:39][CH3:40])=[O:35])[CH2:30][CH2:29]2)[C:9]=1Br.C([Sn](CCCC)(CCCC)[C:62]([O:64][CH2:65][CH3:66])=[CH2:63])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>[CH3:1][Si:2]([CH3:56])([CH3:55])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][N:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:21]=3)=[C:12]2[N:11]=[C:10]([CH:28]2[CH2:33][CH2:32][C:31]([O:41][CH2:42][CH2:43][O:44][CH3:45])([C:34]([O:36][CH2:37][CH2:38][O:39][CH3:40])=[O:35])[CH2:30][CH2:29]2)[C:9]=1[C:62]([O:64][CH2:65][CH3:66])=[CH2:63]

Participants

5

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 866867372-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate

Product 1

HCID 665872102-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate (300 mg, 0.343 mmol), tributyl(1-ethoxyvinyl)tin (0.348 mL, 1.03 mmol), Pd(PPh3)4 (39.6 mg, 0.034 mmol) in dioxane (3.5 mL) was stirred at 100° C. under Ar for 16 h. The reaction mixture was passed through a short SiO2/KF (9:1) plug (eluting with EtOAc) to remove the majority of Tin species. After evaporating, the crude product was purified by a SiO2 column (0-30%, EtOAc/Hexanes, Rf=0.65 in 50% EtOAc) to afford 2-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate as a pale yellow oil (258 mg, 87%).

Workup

  1. washThe reaction mixture was passed through a short SiO2/KF (9:1) plug (eluting with EtOAc)
  2. customto remove the majority of Tin species
  3. customAfter evaporating
  4. customthe crude product was purified by a SiO2 column (0-30%, EtOAc/Hexanes, Rf=0.65 in 50% EtOAc)

Sources & evidence

ORD record
ord-69ce9eec75a643e8b791f5cdd1fa0d53
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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