Triethylamine → HCID 57758009, compound

HRID 229636Notes

Reaction equation

HRID 229636 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20]([NH:22][C:23]4[CH:28]=[C:27]([CH3:29])[CH:26]=[CH:25][N:24]=4)=[O:21])=[CH:15][CH:14]=3)[C:9]([CH2:11][OH:12])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1.S(Cl)(Cl)=O.[CH2:34](N(CC)CC)C>C(Cl)Cl>[NH2:1][C:2]1[C:7]2=[C:8]([C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20]([NH:22][C:23]4[CH:28]=[C:27]([CH3:29])[CH:26]=[CH:25][N:24]=4)=[O:21])=[CH:15][CH:14]=3)[C:9]([CH2:11][O:12][CH3:34])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 57758303HCID 57758303, compound

Product 1

HCID 57758009HCID 57758009, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of DCM (5 mL) was added N-{4-[4-amino-6-(hydroxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-(4-methylpyridin-2-yl)urea (Example 262) (40 mg, 0.10 mmol) followed by 2M thionyl chloride in DCM (0.51 mL, 1.03 mmol). The solution was stirred at rt for 1 h and was then evaporated in vacuo. THF (5 mL) and MeOH (5 mL) were added to the crude reaction followed by triethylamine (43 μL, 0.31 mmol). The solution was heated to 50° C. for 3 d and then evaporated in vacuo and purified by MPLC (Isco) 0-5% MeOH/DCM. The resulting purified fractions were combined and evaporated producing 25 mg of the title compound (0.061 mmol, yield 60%). 1H-NMR (DMSO-d6) δ 10.86 (s, 1H), 9.46 (s, 1H), 8.14 to 8.13 (d, J=6.3 Hz, 1H), 7.84 (s, 1H), 7.75 (s, 1H), 7.65 to 7.63 (d, J=8.7 Hz, 2H), 7.36 to 7.34 (d, J=8.6 Hz, 2H), 7.27 (s, 1H), 6.87 to 6.86 (d, J=5.0 Hz, 1H), 4.27 (s, 2H), 3.20 (s, 3H), 2.30 (s, 3H); MS [M+H]+=404.0; LCMS RT=1.99 min.

Workup

  1. customwas then evaporated in vacuo
  2. additionTHF (5 mL) and MeOH (5 mL) were added to the crude
  3. customreaction
  4. temperatureThe solution was heated to 50° C. for 3 d
  5. customevaporated in vacuo
  6. custompurified by MPLC (Isco) 0-5% MeOH/DCM
  7. customThe resulting purified fractions
  8. customevaporated

Sources & evidence

ORD record
ord-f172c6bbcd564ade96929efb781226b6
Source dataset
uspto-grants-2009_07
Patent number
US07563791B2

Reaction notes

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