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

HRID 2172885
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HRID 2172885 반응식
[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
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 21899848Ethylacetate heptane용매HCID 57417360Sodium chloride; water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-0a486f2be24c474094b2675e2b483b87
출처 데이터셋
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09056865B2

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