4-Methylmorpholine → (2R)-4-[4-(4-Chloro-2-fluorophenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 468633ノート

反応式

HRID 468633 の反応式
CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:31]([F:32])=[CH:30][N:29]([CH2:33][CH2:34][C@@:35]([CH3:43])([S:39]([CH3:42])(=[O:41])=[O:40])[C:36](O)=[O:37])[C:28](=[O:44])[CH:27]=2)=[C:22]([F:45])[CH:21]=1.[O:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH:47]1[O:52][NH2:53]>CC1CCCO1>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:31]([F:32])=[CH:30][N:29]([CH2:33][CH2:34][C@@:35]([CH3:43])([S:39]([CH3:42])(=[O:41])=[O:40])[C:36]([NH:53][O:52][CH:47]3[CH2:48][CH2:49][CH2:50][CH2:51][O:46]3)=[O:37])[C:28](=[O:44])[CH:27]=2)=[C:22]([F:45])[CH:21]=1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70664567(2R)-4-[4-(4-Chloro-2-fluorophenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid

生成物 1

HCID 86670643(2R)-4-[4-(4-Chloro-2-fluorophenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

試薬・触媒・溶媒 1

HCID 73012-Methyltetrahydrofuran溶媒

実験手順

N-Methylmorpholine (54 mL, 491 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (43.1 g, 245 mmol) were added to a solution of (2R)-4-[4-(4-chloro-2-fluorophenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (68.7 g, 164 mmol) in 2-methyltetrahydrofuran (1 L) and the reaction was stirred at rt for 2 h. O-(Tetrahydro-2H-pyran-2-yl)hydroxylamine (28.8 g, 245 mmol) was added and the reaction was allowed to stir at rt for 1 h. The mixture was filtered and the filtrate was concentrated. The crude residue was purified via column chromatography using silica gel and eluting with 40% EtOAc in n-heptane (4 L) and EtOAc (6 L). The desired fractions were combined and concentrated to afford the title compound as a white gummy solid. (74.82 g, 88%). MS (LCMS) m/z 517.9 (M−1).

後処理

  1. stirringto stir at rt for 1 h
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. customThe crude residue was purified via column chromatography
  5. washeluting with 40% EtOAc in n-heptane (4 L) and EtOAc (6 L)
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-ca1b5146dd82417a970313cee26a968d
出典データセット
uspto-grants-2014_01
特許番号
US08624034B2

反応ノート

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