N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoro-methyl)phenyl]urea → HCID 57955332, compound

HRID 73692Notes

Reaction equation

HRID 73692 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH:11]=[O:12])[N:6]2[N:5]=[CH:4][N:3]=1.[CH3:37][Li]>C1COCC1>[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH:11]([OH:12])[CH3:37])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 57955296N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoro-methyl)phenyl]ureaHCID 178418348HCID 178418348, compound

Product 1

HCID 57955332HCID 57955332, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate AW (N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoro-methyl)phenyl]urea (25 mg, 0.05 mmol)) in THF (1 ml) at −78 C under N2 was added methyllithium (0.18 ml, 0.25 mmol) and stirred for 10 min. The reaction was quenched by the addition of H2O and after warming to rt, the reaction mixture was extracted with ethyl acetate. The organic layer was dried (Na2SO4), concentrated and purified via column chromatography (5:95 v/v MeOH—CH2Cl2) to afford 13 mg of the title compound (yield 50%). 1H-NMR (DMSO-d6) δ9.32 (s, 1H), 8.97 (d, J=2 Hz, 1H), 8.63 (dd, J=8, 2 Hz, 1H), 7.87 (s, 1H), 7.55 (d, J=8 Hz, 2H), 7.53 to 7.31 (m, 4H), 5.49 to 5.45 (m, 1H), 5.19 (d, J=6 Hz, 1H), 4.52 (d, J=10 Hz, 1H), 4.19 (d, J=10 Hz, 1H), 3.16 (s, 3H), 1.50 (d, J=6 Hz, 3H) ppm; MS [M+H]+=519.1; LCMS RT=2.74 min.

Workup

  1. customThe reaction was quenched by the addition of H2O
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified via column chromatography (5:95 v/v MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-3a443d6dd6d14b1194205568ec499bc0
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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