Sodium Iodide → HCID 17751773, compound

HRID 1099293Notes

Reaction equation

HRID 1099293 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24]4[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=4[F:34])=[O:22])=[C:16]([F:35])[CH:15]=3)[CH:9]=[C:10]([CH2:11][CH2:12]Br)[N:6]2[N:5]=[CH:4][N:3]=1.[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.C(N(CC)CC)C.[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24]4[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=4[F:34])=[O:22])=[C:16]([F:35])[CH:15]=3)[CH:9]=[C:10]([CH2:11][CH2:12][N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 8083MorpholineHCID 8471TriethylamineHCID 59232072HCID 59232072, compound

Product 1

HCID 17751773HCID 17751773, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of the crude 1-{4-[4-amino-7-(2-bromoethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea (500 mg, crude, 0.331 mmol), morpholine (0.10 ml, 1.12 mmol), triethylamine (0.08 ml, 0.60 mmol) and sodium iodide (7 mg, 0.05 mmol) in 4 ml DMF was heated at 55° C. in a closed vial for 16 h. Cooled to rt, the crude was diluted with 20 ml EtOAc and was washed with aq saturated NaHCO3, brine and dried over Na2SO4. The crude was concentrated and purified via column chromatography (95:5 v/v CH2Cl2—CH3OH) to afford 64 mg of the title compound (yield 47%). 1H-NMR (DMSO-d6 and 1 drop TFA-d) δ 9.44 (d, J=3 Hz, 1H), 9.33(d, J=3 Hz, 1H), 8.65(dd, J=7, 2 Hz, 1H, 8.32(t, J=8 Hz, 1H), 8.15(s, 1H), 7.55-7.51(m, 1H), 7.48-7.24(m, 4H), 6.83(s, 1H), 4.03-4.01 (m, 2H), 3.69-3.49(m, 8H), 3.38-3.33(m, 2H); MS [M+H]+=562.3; LCMS RT=2.84 min.

Workup

  1. temperatureCooled to rt
  2. washwas washed with aq saturated NaHCO3, brine
  3. dry with materialdried over Na2SO4
  4. concentrationThe crude was concentrated
  5. custompurified via column chromatography (95:5 v/v CH2Cl2—CH3OH)

Sources & evidence

ORD record
ord-485098113afd47099b3c6544ebd7060c
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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