4-Methylmorpholine → HCID 59402508, compound

HRID 655766Notes

Reaction equation

HRID 655766 reaction equation
[Cl:1][C:2]1[C:3]([C:11]#[N:12])=[C:4]([C:8]([OH:10])=O)[NH:5][C:6]=1[CH3:7].[NH2:13][C@@H:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][C@@H:15]1[O:25][CH2:26][CH3:27].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[Cl:1][C:2]1[C:3]([C:11]#[N:12])=[C:4]([C:8]([NH:13][C@@H:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][C@@H:15]2[O:25][CH2:26][CH3:27])=[O:10])[NH:5][C:6]=1[CH3:7]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54237477Ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate2×HCID 594025744-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid2×

Product 1

HCID 59402508HCID 59402508, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 16, 1.01 g, 5.55 mmol) and ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate (Intermediate 24, 1.2 g, 5.55 mmol) in dichloromethane (480 mL) were added HOBt (850 mg, 5.55 mmol) and N-methyl morpholine (1.82 mL, 16.66 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (1.9 g, 9.99 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 flash column chromatography (silica, 35% ethylacetate in pet ether) afforded ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate 1.5 g (71%) as 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 flash column chromatography (silica, 35% ethylacetate in pet ether)

Sources & evidence

ORD record
ord-814d39b06bed4570a280b9a8a9478c0e
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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