Sodium Hydroxide → HCID 78322881, compound

HRID 336168

Reaction equation

HRID 336168 reaction equation
B1(B2C3CCCC2CCC3)C2CCCC1CCC2.[NH2:19][C:20]1[C:21]2[C:28]([C:29]3[CH:30]=[N:31][C:32]4[C:37]([CH:38]=3)=[CH:36][CH:35]=[CH:34][CH:33]=4)=[C:27](Br)[N:26]([CH2:40][C@@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH:42]=[CH2:43])[C:22]=2[N:23]=[CH:24][N:25]=1.[OH-].[Na+]>O1CCCC1>[NH2:19][C:20]1[C:21]2[C:28]([C:29]3[CH:30]=[N:31][C:32]4[C:37]([CH:38]=3)=[CH:36][CH:35]=[CH:34][CH:33]=4)=[C:27]3[N:26]([C:22]=2[N:23]=[CH:24][N:25]=1)[CH2:40][C@@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:42][CH2:43]3

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 113224419-Borabicyclo[3.3.1]nonane dimerHCID 86711295HCID 86711295, compound

Product 1

HCID 78322881HCID 78322881, compoundYield 80.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

9-Borabicyclo[3.3.1]nonane dimer (0.431 g) was added to a solution of (S)-tert-butyl (1-(4-amino-6-bromo-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate (0.3 g) obtained in Reference Example 1 in tetrahydrofuran (4.5 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at room temperature for 2 hours. A 4 N sodium hydroxide aqueous solution (2.12 ml) was slowly added to the reaction mixture at room temperature, and degassed under reduced pressure. Under a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (0.136 g) was added to the resulting mixture, and stirred at 64° C. for 12 hours. After the reaction mixture was cooled, and diluted with ethyl acetate, a saturated ammonium chloride aqueous solution was added thereto. After the insoluble matter resulting in this stage was removed by filtration, the organic layer was separated. The resulting organic layer was dried over anhydrous sodium sulfate, then filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain (S)-tert-butyl (4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)carbamate (203 mg) (yield: 80%) as a light-yellow solid.

Workup

  1. customdegassed under reduced pressure
  2. additionUnder a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (0.136 g) was added to the resulting mixture
  3. stirringstirred at 64° C. for 12 hours
  4. temperatureAfter the reaction mixture was cooled
  5. additiondiluted with ethyl acetate
  6. additiona saturated ammonium chloride aqueous solution was added
  7. customAfter the insoluble matter resulting in this stage
  8. customwas removed by filtration
  9. customthe organic layer was separated
  10. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto obtain a crude product
  14. customThe crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol)

Sources & evidence

ORD record
ord-ce9894e6a95d409bb07056741c97bcee
Source dataset
uspto-grants-2014_11
Patent number
US08889666B2

Linked notes

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