Sodium Hydroxide → HCID 86711290, compound

HRID 336155Notes

Reaction equation

HRID 336155 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[N:13][C:14]4[C:19]([CH:20]=3)=[CH:18][CH:17]=[CH:16][CH:15]=4)=[C:9](Br)[N:8]([CH2:22][CH2:23][C@@H:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:25]=[CH2:26])[C:4]=2[N:5]=[CH:6][N:7]=1.C12BC(CCC1)CCC2.[OH-].[Na+]>C1COCC1.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>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[N:13][C:14]4[C:19]([CH:20]=3)=[CH:18][CH:17]=[CH:16][CH:15]=4)=[C:9]3[CH2:26][CH2:25][C@H:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:23][CH2:22][N:8]3[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 86711289HCID 86711289, compound

Product 1

HCID 86711290HCID 86711290, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(R)-tert-Butyl (5-(4-amino-6-bromo-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pent-1-en-3-yl)carbamate (994 mg) obtained in Step 7 was added to a solution of 9-borabicyclo[3.3.1]nonane in 0.5 M THF (22.8 ml) at room temperature. The mixture was stirred at the same temperature for 1 hour, and a 4 N aqueous sodium hydroxide solution (5.7 ml) was carefully added thereto. After nitrogen purging, the mixture was heated to have an internal temperature of 55° C. Tetrakis(triphenylphosphine)palladium (275 mg) was added thereto, and the mixture was stirred at an internal temperature of 66° C. for 15 hours. After cooling the reaction mixture, the organic layer was separated, and toluene (7.7 ml) and a 20% aqueous ammonium chloride solution (5 ml) were added thereto. The organic layer was separated, washed with a 20% saline solution, and SH silica gel (produced by Fuji Silysia, 1 g) was added thereto. The mixture was stirred at an internal temperature 68° C. for 1 hour, and SH silica gel (produced by Fuji Silysia, 1 g) was added thereto. The mixture was stirred at an internal temperature of 68° C. for 1 hour. After cooling, the silica gel was filtered off, and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain the title compound as a yellow solid (439 mg).

Workup

  1. temperatureAfter nitrogen purging, the mixture was heated
  2. customan internal temperature of 55° C
  3. stirringthe mixture was stirred at an internal temperature of 66° C. for 15 hours
  4. temperatureAfter cooling the reaction mixture
  5. customthe organic layer was separated
  6. additiontoluene (7.7 ml) and a 20% aqueous ammonium chloride solution (5 ml) were added
  7. customThe organic layer was separated
  8. washwashed with a 20% saline solution, and SH silica gel (produced by Fuji Silysia, 1 g)
  9. additionwas added
  10. stirringThe mixture was stirred at an internal temperature 68° C. for 1 hour
  11. additionSH silica gel (produced by Fuji Silysia, 1 g) was added
  12. stirringThe mixture was stirred at an internal temperature of 68° C. for 1 hour
  13. temperatureAfter cooling
  14. filtrationthe silica gel was filtered off
  15. distillationthe solvent was distilled off under reduced pressure
  16. customThe resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol)

Sources & evidence

ORD record
ord-e5844bc60fde49b990ab2bc19faf549f
Source dataset
uspto-grants-2014_11
Patent number
US08889666B2

Reaction notes

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