4-Methylmorpholine → N-(1-(5'-chloro-3'-fluoro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperidin-4-yl)-3-(methylsulfonyl)propanamide

HRID 2172885Notes

Reaction equation

HRID 2172885 reaction equation
[Cl:1][C:2]1[C:3]([C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=2)=[C:4]([F:15])[C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH3:24][S:25]([CH2:28][CH2:29][C:30](O)=[O:31])(=[O:27])=[O:26].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.[Cl-].[Na+].O.CCCCCCC.CCOC(C)=O.CCOC(C)=O>[Cl:1][C:2]1[C:3]([C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=2)=[C:4]([F:15])[C:5]([N:8]2[CH2:9][CH2:10][CH:11]([NH:14][C:30](=[O:31])[CH2:29][CH2:28][S:25]([CH3:24])(=[O:27])=[O:26])[CH2:12][CH2:13]2)=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 79724-MethylmorpholineHCID 1203083-(Methylsulfonyl)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 690435731-(5'-Chloro-3'-fluoro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperidin-4-amine

Product 1

HCID 86691911N-(1-(5'-chloro-3'-fluoro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperidin-4-yl)-3-(methylsulfonyl)propanamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A stirred solution of 1-(5′-chloro-3′-fluoro-3,5-dimethyl-[2,4′-bipyridin]-2′-yl)piperidin-4-amine (81.5 mg, 0.20 mmol), 3-(methylsulfonyl)propanoic acid (45.7 mg. 0.30 mmol), and NMM (80.9 mg, 0.80 mmol) in DMF (2 mL) was treated with HATU (91.3 mg, 0.24 mmol) portionwise. The reaction solution was stirred at rt under nitrogen for 2 h. EtOAc (30 mL) and brine (10 mL) were added and layers were separated. The organic layer was washed with brine (2×), dried over sodium sulfate, and concentrated. Purification on ISCO separation system with a 4-gram column using 0-8% MeOH in EtOAc afforded a colorless gum, which was sonicated in heptane/EtOAc to furnish a solid. After solvent removal, 56 mg (60%) of waxy, white solid was obtained: LRMS (M+H)+: 469.1; 1H NMR (400 MHz, CDCl3) δ 1.52 (dd, J=12.51, 3.66 Hz, 2 H), 2.02 (d, J=12.38 Hz, 2 H), 2.15 (s, 3 H), 2.39 (s, 3 H), 2.74 (t, J=6.95 Hz, 2 H), 2.96 (s, 3 H), 2.97-3.12 (m, 2 H), 3.42 (t, J=7.07 Hz, 2 H), 3.89-4.12 (m, 3 H), 5.63 (d, J=7.33 Hz, 1H), 7.47 (d, J=0.76 Hz, 1 H), 8.10 (s, 1 H), 8.40 (d, J=1.26 Hz, 1 H).

Workup

  1. customlayers were separated
  2. washThe organic layer was washed with brine (2×)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customPurification
  6. customon ISCO separation system with a 4-gram column
  7. customafforded a colorless gum, which
  8. customto furnish a solid
  9. customAfter solvent removal, 56 mg (60%) of waxy
  10. customwhite solid was obtained

Sources & evidence

ORD record
ord-0a486f2be24c474094b2675e2b483b87
Source dataset
uspto-grants-2015_06
Patent number
US09056865B2

Reaction notes

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