4-Methylmorpholine → methyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidine-1-carboxylate

HRID 655773ノート

反応式

HRID 655773 の反応式
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([OH:11])=O.[NH2:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][C@@H:14]1[CH3:23].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][C@@H:14]1[CH3:23])=[O:11]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 251376823,4-Dichloro-5-methyl-1H-pyrrole-2-carboxylic acidHCID 58075083Methyl (3S,4R)-4-amino-3-methylpiperidine-1-carboxylate2 回

生成物 1

HCID 59402510methyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidine-1-carboxylate収率 67.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 3,4-dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (WO2006087543. 2.8 g, 14.53 mmol) and methyl (3S,4R)-4-amino-3-methylpiperidine-1-carboxylate (Intermediate 37, 2.5 g, 14.53 mmol) in dichloromethane (200 mL) was added HOBT (2.22 g, 14.53 mmol) and N-methyl morpholine (4.82 mL, 43.60 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (5.12 g, 26.16 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with 2N hydrochloric acid (120 mL). The organic layer was washed with sodium bicarbonate (150 mL), water (150 mL), and brine, dried over anhydrous sodium sulphate, filtered, concentrated under vacuum. Purification by column chromatography (silica, 35% ethylacetate in pet ether) afforded methyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidine-1-carboxylate 3.4 g (67%) as brown solid.

後処理

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. customThe reaction mixture was quenched with 2N hydrochloric acid (120 mL)
  4. washThe organic layer was washed with sodium bicarbonate (150 mL), water (150 mL), and brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customPurification by column chromatography (silica, 35% ethylacetate in pet ether)

出典と根拠

ORDレコード
ord-0cfa7d3cd5f54239b075c604a8d4fb64
出典データセット
uspto-grants-2011_12
特許番号
US08071605B2

反応ノート

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