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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
ノート
印刷プレビュー

反応式

HRID 2172885 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 21899848Ethylacetate heptane溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-0a486f2be24c474094b2675e2b483b87
出典データセット
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09056865B2

反応ノート

読み込み中…

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