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

HRID 655761노트

반응식

HRID 655761 반응식
[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]

참가 물질

7

반응물 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-carboxylate2회

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-4990a75df83641d79fdd664db5cfc457
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071605B2

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