Iodine → HCID 57444149, compound

HRID 875134Notes

Reaction equation

HRID 875134 reaction equation
N[C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6]3[C:12]([C:16]([NH:18][C@@H:19]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[O:17])=[N:13][N:14]([CH3:15])[C:5]=3[C:4]=2[N:3]=1.[I-:33].[Cs+].II.N(OCCC(C)C)=O>C(COC)OC.[Cu](I)I>[I:33][C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6]3[C:12]([C:16]([NH:18][C@@H:19]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)=[O:17])=[N:13][N:14]([CH3:15])[C:5]=3[C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 807IodineHCID 8053Isoamyl NitriteHCID 24601Cesium iodideHCID 574441508-amino-1-methyl-N-[(1S)-2-morpholin-4-yl-1-phenylethyl]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

Product 1

HCID 57444149HCID 57444149, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a well stirred and warm suspension of 8-amino-1-methyl-N-[(1S)-2-morpholin-4-yl-1-phenylethyl]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (3 g, 6.92 mmol) in dimethoxyethane (240 mL), maintained in an inert atmosphere of argon, cesium iodide (2.16 g, 8.3 mmol), bisublimated iodine (870 mg, 3.46 mmol), copper iodide (460 mg, 2.42 mmol) and isopentyl nitrite (1.71 mL, 1.5 g, 12.46 mmol) were added, in sequence. The reaction mixture was stirred vigorously at 65-70° C. for 18 hours. After cooling in an ice-water bath, the solid was filtered off and the filtrate was diluted with dichloromethane (100 mL), washed with 30% ammonium hydroxide (50 mL), sodium thiosulphate (100 mL), brine and dried over anhydrous Na2SO4. The crude was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95:59) and 1.48 g of the title compound was isolated (40% yield).

Workup

  1. temperaturewarm
  2. additionwere added, in sequence
  3. stirringThe reaction mixture was stirred vigorously at 65-70° C. for 18 hours
  4. temperatureAfter cooling in an ice-water bath
  5. filtrationthe solid was filtered off
  6. additionthe filtrate was diluted with dichloromethane (100 mL)
  7. washwashed with 30% ammonium hydroxide (50 mL), sodium thiosulphate (100 mL), brine
  8. dry with materialdried over anhydrous Na2SO4
  9. customThe crude was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95:59)

Sources & evidence

ORD record
ord-a66929b05d5c46d2b1df2f0d4e403f82
Source dataset
uspto-grants-2015_03
Patent number
US08981089B2

Reaction notes

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