Sodium Iodide → HCID 59232042, compound

HRID 1099260Notes

Reaction equation

HRID 1099260 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:12][CH2:13][CH2:14]Br)[N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(N(CC)CC)C.[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:12][CH2:13][CH2:14][N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 8083MorpholineHCID 8471TriethylamineHCID 59231920HCID 59231920, compound

Product 1

HCID 59232042HCID 59232042, compoundYield 48.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-bromo-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (931 mg, 2.78 mmol), morpholine (1.214 g, 13.94 mmol, 5.0 eq), triethylamine (1.16 ml, 8.36 mmol, 3.0 eq), and sodium iodide (63 mg, 0.42 mmol, 0.15 eq) in anhydrous DMF (20 mL) was stirred at 55° C. for 17 h. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 followed by saturated brine. It was dried over Na2SO4, filtered, concentrated at reduced pressure to first remove EtOAc followed by some DMF with pumping. The crude was dissolved in THF and then preloaded by evaporation onto about 5 ml silica gel and then chromatographed on 40 g silica gel using a gradient from 0-10% MeOH in CH2Cl2 to provide 457 mg (47.9%) of the desired product as a white solid along with another 435 mg (46%) of mixed fractions contaminated with the dibromide which came from the tribromide contaminant in the starting material as noted above in step 4. 1H-NMR (DMSO-d6) 7.86 (s, 1H), 6.65 (s, 1H), 3.56 (t, 4H, J=4.6), 2.84 (t, 2H), 2.25-2.35 (m, 6H), and 1.80 (pent, 2H, J=7.4); MS LC-MS [M+H]+=340.2/342.2, RT=1.09 min.

Workup

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialIt was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated at reduced pressure to first remove EtOAc
  5. dissolutionThe crude was dissolved in THF
  6. custompreloaded by evaporation onto about 5 ml silica gel
  7. customchromatographed on 40 g silica gel using a gradient from 0-10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-7b0b9f89c190490d8b597db92342cdbd
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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