4-Methylmorpholine → 1-(3-Fluoro-2'-methanesulfonyl-biphenyl-4-yl)-3-[3-(5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl)-phenylamino]-piperidin-2-one

HRID 50041

Reaction equation

HRID 50041 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[S:30]([CH3:33])(=[O:32])=[O:31])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=2)[C:18]#[N:19])[C:9]1=[O:23].C(C1C=C(C=CC=1)N)#N.Cl.N[NH:45][C:46]([NH2:48])=[O:47].CN1CCOCC1>C(Cl)(Cl)Cl.CO>[F:1][C:2]1[CH:3]=[C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[S:30]([CH3:33])(=[O:31])=[O:32])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][C:15]2[CH:22]=[CH:21][CH:20]=[C:17]([C:18]3[NH:48][C:46](=[O:47])[NH:45][N:19]=3)[CH:16]=2)[C:9]1=[O:23]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 11236Semicarbazide hydrochlorideHCID 167023-AminobenzonitrileHCID 691425583-[1-(3-Fluoro-2'-methanesulfonyl-biphenyl-4-yl)-2-oxo-piperidin-3-ylamino]-benzonitrile

Product 1

HCID 1354861221-(3-Fluoro-2'-methanesulfonyl-biphenyl-4-yl)-3-[3-(5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl)-phenylamino]-piperidin-2-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

A sample of 3-[1-(3-fluoro-2′-methanesulfonyl-biphenyl-4-yl)-2-oxo-piperidin-3-ylamino]-benzonitrile, prepared from the compound of Ex. 1, part A and 3-cyanoaniline according to the procedure of Ex. 1, Part B, was suspended in a 2:1 mixture of anhydrous MeOH and chloroform and cooled in a 0° C. ice-bath. HCl gas was then bubbled in the mixture for 30 minutes resulting in a clear solution. The reaction vessel was sealed and stored at 0° C. for 18 hours. The mixture was concentrated in vacuo and dried. The resulting residue was suspended in 1,4-dioxane. Semicarbazide hydrochloride (1.7 eq) was then added, followed by N-methylmorpholine (7.2 eq). The mixture was refluxed for 48 hours. The precipitate was filtered and washed with 1,4-dioxane, water, and ether. The solid was pumped dry to afford the title compound. 1H NMR (DMSO-d6, 300 MHz) δ 11.87 (s, 1H), 11.56 (s, 1H), 8.11(d, J=8.1 Hz, 1H), 7.75 (m, 2H), 7.47 (m, 2H), 7.37 (d, J=11.0 Hz, 1H), 7.29 (d, J=7.9 Hz, 1H), 7.15 (t, J=7.9 Hz, 1H), 7.08 (br m, 1H), 6.96 (d, J=7.3 Hz, 1H), 6.78 (br d, J=9.5 Hz, 1H), 4.28 (m, 1H), 3.73 (t, J=6.2 Hz, 2H), 2.90 (s, 3H), 2.30 (m, 1H), 2.10 (m, 2H), 1.90 (m, 1H); MS ESI (M+H) 522.4.

Workup

  1. customHCl gas was then bubbled in the mixture for 30 minutes
  2. customresulting in a clear solution
  3. customThe reaction vessel was sealed
  4. concentrationThe mixture was concentrated in vacuo
  5. customdried
  6. temperatureThe mixture was refluxed for 48 hours
  7. filtrationThe precipitate was filtered
  8. washwashed with 1,4-dioxane, water, and ether
  9. customThe solid was pumped dry

Sources & evidence

ORD record
ord-1458d5911796401f9ee2a06bf3bfc299
Source dataset
uspto-grants-2004_03
Patent number
US06710058B2

Linked notes

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