1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

HRID 12233Notes

Reaction equation

HRID 12233 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[CH2:20][N:19]3[CH2:26][CH:27]([NH2:31])[CH:28]([CH3:30])[CH3:29])=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.[CH3:32][C:33]1[N:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35](O)=[O:36].CCN=C=NCCCN(C)C>N1C=CC=CC=1.O.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[CH2:23][O:22][C:21]([CH3:24])([CH3:25])[CH2:20][N:19]3[CH2:26][CH:27]([NH:31][C:35]([C:34]3[C:33]([CH3:32])=[N:41][CH:40]=[CH:39][CH:38]=3)=[O:36])[CH:28]([CH3:29])[CH3:30])=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1

Participants

7

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 6433732-Methylnicotinic acidHCID 671651234-(2-amino-3-methyl-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

Product 1

HCID 671657436,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amideYield 77%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(2-amino-3-methyl-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide (1.47 g, 3.31 mmol) in pyridine (35 mL) was added 2-methyl-nicotinic acid (544 mg, 3.97 mmol) and EDCI (1.02 g, 5.30 mmol). The solution was stirred 6.5 hours at room temperature, then diluted with water (100 mL). The mixture was poured into a separatory funnel and diluted further with water (50 mL) and EtOAc (150 mL). The layers were shaken and separated. The aqueous layer was extracted with EtOAc (3×50 mL), then the combined organic layers were washed with brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to yield an orange semi-solid residue which was purified via column chromatography. The resulting yellow solid was placed on the high-vacuum pump overnight, after which 1.43 g of 6,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide was obtained (77% yield).

Workup

  1. additionThe mixture was poured into a separatory funnel
  2. stirringThe layers were shaken
  3. customseparated
  4. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  5. washthe combined organic layers were washed with brine
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield an orange semi-solid residue which
  10. customwas purified via column chromatography
  11. customwas placed on the high-vacuum pump overnight

Sources & evidence

ORD record
ord-8c05c8b7442241ab9e8f8efb8e990e3f
Source dataset
uspto-grants-2010_06
Patent number
US07727985B2

Reaction notes

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