Nitrogen → HCID 86686744, compound

HRID 2369022Notes

Reaction equation

HRID 2369022 reaction equation
[CH3:1][Si:2]([CH3:52])([CH3:51])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH:28]([NH:30][C:31]([C:33]2([CH3:41])[CH2:38][O:37][C:36]([CH3:40])([CH3:39])[O:35][CH2:34]2)=[O:32])[CH3:29])[C:9]=1Br.N#N.C([Sn](CCCC)(CCCC)[C:60]([O:62][CH2:63][CH3:64])=[CH2:61])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.O1CCOCC1>[CH3:1][Si:2]([CH3:52])([CH3:51])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH:28]([NH:30][C:31]([C:33]2([CH3:41])[CH2:38][O:37][C:36]([CH3:40])([CH3:39])[O:35][CH2:34]2)=[O:32])[CH3:29])[C:9]=1[C:60]([O:62][CH2:63][CH3:64])=[CH2:61]

Participants

6

Reactant 3

HCID 947NitrogenHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 86686742HCID 86686742, compound

Product 1

HCID 86686744HCID 86686744, compoundYield 83.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

N-{1-[7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-6-bromo-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl]ethyl}-2,2,5-trimethyl-1,3-dioxane-5-carboxamide (63.7 mg, 0.078 mmol) and tetrakis(triphenylphosphine)palladium(0) (9.0 mg, 0.0078 mmol) were combined in a microwave tube, and the cap was crimped on. The headspace was purged with dry N2 (×2), and tributyl[1-(ethyloxy)ethenyl]stannane (53 μL, 0.16 mmol) and 1,4-dioxane (0.69 mL) were added. The suspension was sparged with dry N2 for ca. 3 min. The tube was lowered into a pre-heated 100° C. oil bath and stirred over night. The dark reaction mixture was then cooled, partitioned between aq. KF (2 mL, 0.5 M) and ether (ca. 3 mL). The layers were separated, and the aqueous was extracted with ether (1×3 mL), the organics were combined, washed with brine (2 mL), dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude matrial (105 mg) was adsorbed into silica gel, and purified by flash chromatography (15 g silica, hexanes to 25% EtOAc in hexanes, the 5% MeOH in DCM). Like fractions were combined, and concentrated to give N-{1-[7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-6-(1-ethoxyvinyl)-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl]ethyl}-2,2,5-trimethyl-1,3-dioxane-5-carboxamide (52.5 mg, 83%) as a yellow film. The material contained a small amount of triphenylphosphine oxide, and carried on as is.

Workup

  1. additionwere added
  2. customThe suspension was sparged with dry N2 for ca. 3 min
  3. customwas lowered into a pre-heated 100° C.
  4. customThe dark reaction mixture
  5. temperaturewas then cooled
  6. custompartitioned between aq. KF (2 mL, 0.5 M) and ether (ca. 3 mL)
  7. customThe layers were separated
  8. extractionthe aqueous was extracted with ether (1×3 mL)
  9. washwashed with brine (2 mL)
  10. dry with materialdried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. custompurified by flash chromatography (15 g silica, hexanes to 25% EtOAc in hexanes
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-a9e90b7208184389b6b6dab4bb2d3d14
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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