4-Aminopyridine → HCID 89714592, compound

HRID 2273072Notes

Reaction equation

HRID 2273072 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:18]3[C:17](=[O:19])[N:16]([CH2:20][CH3:21])[CH2:15][C:14]([CH3:23])([CH3:22])[O:13][C:12]=3[N:11]=[C:10]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]3[CH3:30])[N:9]=2)=[C:4]([F:31])[CH:3]=1.CCN(C(C)C)C(C)C.[C:41](Cl)(Cl)=[O:42].[NH2:45][C:46]1[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=1>O1CCOCC1.C1(C)C=CC=CC=1.CN(C=O)C.O>[CH2:20]([N:16]1[CH2:15][C:14]([CH3:22])([CH3:23])[O:13][C:12]2[N:11]=[C:10]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]3[CH3:30])[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:41]([NH:45][C:46]4[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=4)=[O:42])=[CH:3][C:4]=3[F:31])[C:18]=2[C:17]1=[O:19])[CH3:21]

Participants

9

Reactant 4

HCID 17274-AminopyridineHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 89714709HCID 89714709, compound

Product 1

HCID 89714592HCID 89714592, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

150 mg (394 μmol) of 4-(4-amino-2-fluorophenyl)-6-ethyl-8,8-dimethyl-2-((S)-3-methylmorpholin-4-yl)-7,8-dihydro-6H-9-oxa-1,3,6-triazabenzocyclohepten-5-one are suspended in 4 ml anhydrous dioxane under argon. 92 μl (524 μmol) of DIEA are added, followed by 276 μl of a 1.9M solution of phosgene in toluene, after which the mixture is heated at 50° C. for 30 minutes. The resulting mixture is allowed to cool, followed by addition of 202 mg (2.10 mmol) of 4-aminopyridine dissolved in 2 ml of anhydrous DMF. The resulting mixture is reacted for 3 hours. It is poured into water, stirred, filtered and washed with water. The product is dissolved in DCM, dried over Na2SO4 and then concentrated under reduced pressure. It is taken up in Et2O, and the mixture is stirred and filtered. The product is dissolved in 5 ml of DCM with a small amount of MeOH, and 20 ml of ethyl acetate are added. The product is placed in a refrigerator and the solid is then filtered off to give 146 mg of 1-{4-[6-ethyl-8,8-dimethyl-2-((S)-3-methylmorpholin-4-yl)-5-oxo-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]-3-fluorophenyl}-3-pyridin-4-ylurea.

Workup

  1. temperatureto cool
  2. customThe resulting mixture is reacted for 3 hours
  3. filtrationfiltered
  4. washwashed with water
  5. dissolutionThe product is dissolved in DCM
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. stirringthe mixture is stirred
  9. filtrationfiltered
  10. dissolutionThe product is dissolved in 5 ml of DCM with a small amount of MeOH, and 20 ml of ethyl acetate
  11. additionare added
  12. filtrationthe solid is then filtered off

Sources & evidence

ORD record
ord-10cb7b1463544d5cb07d3ad99c96ed20
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

Loading…