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

HRID 655773Notes

Reaction equation

HRID 655773 reaction equation
[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]

Participants

7

Reactant 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×

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-0cfa7d3cd5f54239b075c604a8d4fb64
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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