4-Methylmorpholine → HCID 59402444, compound

HRID 655758Notes

Reaction equation

HRID 655758 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][CH:27]=[CH2:28].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][CH:27]=[CH2:28])=[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 58075108Ethyl (3S,4R)-4-amino-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate2×HCID 594025744-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid2×

Product 1

HCID 59402444HCID 59402444, compoundYield 90.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 16, 562 mg, 3.07 mmol) and ethyl (3S,4R)-4-amino-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate (Intermediate 18, 700 mg, 3.07 mmol) in dichloromethane (150 mL) were added HOBt (470 mg, 3.07 mmol) and N-methyl morpholine (1.01 mL, 9.21 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (1.05 g, 5.52 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with the addition of 2 N HCl (100 mL). The organic layer was washed with sodium bicarbonate (150 mL), water (150 mL) and brine, and dried over anhydrous sodium sulphate, filtered, and concentrated under vacuum. Purification by column chromatography (silica, 35% ethyl acetate in pet ether) afforded Ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate 1.1 g (90%) as brown solid.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. customThe reaction mixture was quenched with the addition of 2 N HCl (100 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% ethyl acetate in pet ether)

Sources & evidence

ORD record
ord-100208ae946a43de8bb1e39567c7bfa6
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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