Ammonia → HCID 86710424, compound

HRID 1398443Notes

Reaction equation

HRID 1398443 reaction equation
[F-].[K+].I[C:4]1[C:20]([O:21][CH2:22][C@@H:23]([N:28]2[C:36](=[O:37])[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:29]2=[O:38])[CH2:24][CH:25]([CH3:27])[CH3:26])=[CH:19][C:7]2[N:8]([CH3:18])[C:9](=[O:17])[C:10]3[C:15]([C:6]=2[CH:5]=1)=[CH:14][CH:13]=[N:12][C:11]=3[CH3:16].C[Si](C)(C)[C:41]([F:44])([F:43])[F:42].N>[Cu]I.CN1CCCC1=O>[CH3:16][C:11]1[N:12]=[CH:13][CH:14]=[C:15]2[C:10]=1[C:9](=[O:17])[N:8]([CH3:18])[C:7]1[CH:19]=[C:20]([O:21][CH2:22][C@@H:23]([N:28]3[C:29](=[O:38])[C:30]4[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:36]3=[O:37])[CH2:24][CH:25]([CH3:27])[CH3:26])[C:4]([C:41]([F:44])([F:43])[F:42])=[CH:5][C:6]2=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 522689Potassium FluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 86710422HCID 86710422, compound

Product 1

HCID 86710424HCID 86710424, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
200 °C

Procedure

Dried potassium fluoride (19.51 mg, 0.336 mmol) and copper(I) iodide (64.0 mg, 0.336 mmol) were mixed and heated to 200° C. under gentle shaking at reduced pressure (1 Torr) until a light yellow-greenish color appeared. After cooling, anhydrous N-methyl-2-pyrrolidinone (1 mL) was added, followed by (S)-2-(1-((9-iodo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (100 mg, 0.168 mmol) and trimethyl(trifluoromethyl)silane (0.075 mL, 0.504 mmol). The brown solution thus obtained was heated at 90° C. for 16 h. After cooling, aqueous ammonia (10 mL) was added to the reaction mixture. The reaction mixture was and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (1×10 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative TLC (50% ethyl acetate: petroleum ether as eluent system) to afford (S)-2-(1-(4,6-dimethyl-5-oxo-9-(trifluoromethyl)-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yloxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (80 mg, 0.033 mmol, 20% yield, 22% purity) as a pale yellow solid. LC/MS (ESI) m/e 538.6 [(M+H)+, calcd for C29H27F3N3O4 538.2] LC/MS retention time (method E): tR=1.27 min.

Workup

  1. temperatureAfter cooling
  2. customThe brown solution thus obtained
  3. temperaturewas heated at 90° C. for 16 h
  4. temperatureAfter cooling
  5. extractionextracted with ethyl acetate (3×10 mL)
  6. washThe combined organic layers were washed with brine (1×10 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative TLC (50% ethyl acetate: petroleum ether as eluent system)

Sources & evidence

ORD record
ord-c36057918ce54750b7f72af1f1c3b5e5
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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