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

HRID 655761ノート

反応式

HRID 655761 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][CH2:22][CH3:23])=[O:20])[CH2:15][C@@H:14]1[O:24][CH2:25][CH3:26].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][CH2:22][CH3:23])=[O:20])[CH2:15][C@@H:14]1[O:24][CH2:25][CH3:26])=[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 54237477Ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate2 回

生成物 1

HCID 59402472ethyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate収率 78.8%

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 (WO200687543, 1.18 g, 6.15 mmol) and ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate (Intermediate 24, 1.33 g, 6.15 mmol) in dichloromethane (170 mL) were added HOBT (941 mg, 6.15 mmol) and N-methyl morpholine (2.02 mL, 18.45 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (2.11 g, 11.07 mmol) was added. The resulting reaction mixture was stirred for room temperature overnight. The reaction was quenched with the addition of 2N HCl (120 mL). The organic layer was washed with sodium bicarbonate (150 mL), water (150 mL), and brine, and dried over anhydrous sodium sulphate, filtered, concentrated under vacuum. Purification by flash column chromatography (silica, 35% ethylacetate in pet ether) afforded ethyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate 1.9 g (49%) as solid.

後処理

  1. customThe resulting reaction mixture
  2. stirringwas stirred for room temperature overnight
  3. customThe reaction was quenched with the addition of 2N HCl (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 flash column chromatography (silica, 35% ethylacetate in pet ether)

出典と根拠

ORDレコード
ord-4990a75df83641d79fdd664db5cfc457
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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