Ammonia → HCID 73776648, compound

HRID 1052687Notes

Reaction equation

HRID 1052687 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([NH:17][C@H:18]([C:20]4[N:25]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)[C:24](=[O:32])[C:23]5=[C:33]([CH3:36])[CH:34]=[CH:35][N:22]5[N:21]=4)[CH3:19])=[N:14][CH:13]=[N:12][C:11]=3[N:10](COCC[Si](C)(C)C)[CH:9]=2)=[C:4]([O:45]C)[CH:3]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+].N>ClCCl.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([NH:17][C@H:18]([C:20]4[N:25]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)[C:24](=[O:32])[C:23]5=[C:33]([CH3:36])[CH:34]=[CH:35][N:22]5[N:21]=4)[CH3:19])=[N:14][CH:13]=[N:12][C:11]=3[NH:10][CH:9]=2)=[C:4]([OH:45])[CH:3]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 131736249HCID 131736249, compound

Product 1

HCID 73776648HCID 73776648, compoundYield 54.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-2-(1-((5-(4-Fluoro-2-methoxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (65 mg, 0.10 mmol) was dissolved in 1.3 ml dichloromethane and the reaction mixture was cooled at 0aC. Boron tribromide (1M in dichloromethane, 1 mL, 1.02 mmol) was added dropwise and the reaction mixture was stirred overnight. The reaction mixture was poured into a 4% sodium bicarbonate solution and extracted twice with dichloromethane. The organics were combined, dried, filtered and concentrated under reduced pressure. The white solid formed was re-dissolved in 650 μl anhydrous methanol and ammonia solution (7M in methanol, 1.3 ml, 9.1 mmol) was added. The reaction mixture was stirred at room temperature for 2 h and then concentrated to dryness, suspended in water and extracted twice with ethyl acetate. The organics were combined, dried over sodium sulphate, filtered and evaporated under reduced pressure. The crude was purified using SP1® Purification System (0% to 10%, hexane-ethyl acetate) to obtain 27 mg (53% yield) of the title compound as a white solid. Purity 96%.

Workup

  1. temperaturethe reaction mixture was cooled at 0aC
  2. extractionextracted twice with dichloromethane
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe white solid formed
  7. stirringThe reaction mixture was stirred at room temperature for 2 h
  8. concentrationconcentrated to dryness
  9. extractionextracted twice with ethyl acetate
  10. dry with materialdried over sodium sulphate
  11. filtrationfiltered
  12. customevaporated under reduced pressure
  13. customThe crude was purified
  14. customSP1® Purification System (0% to 10%, hexane-ethyl acetate)

Sources & evidence

ORD record
ord-a6499dfd0189440d9b5d5aff30600b76
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

Loading…