Dimethylformamide → HCID 59976407, compound

HRID 2269762Notes

Reaction equation

HRID 2269762 reaction equation
[CH2:1]1[CH2:5]O[CH2:3][CH2:2]1.[C:6](Cl)(=O)[C:7](Cl)=O.C1C2C(COC([NH:29][C@@H:30]([C:41]([OH:43])=O)[CH2:31][C:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[NH:34][CH:33]=3)=O)C3C(=CC=CC=3)C=2C=CC=1.[CH3:44][N:45]([CH:47]=O)[CH3:46]>>[NH2:29][C@H:30]([CH2:31][C:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[NH:34][CH:33]=1)[C:41]([N:29]1[C:30]2[C:5](=[CH:39][CH:40]=[CH:32][CH:31]=2)[CH2:1][CH:2]([CH2:44][N:45]2[CH2:47][CH2:7][CH2:6][CH2:46]2)[CH2:3]1)=[O:43]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8028Tetrahydrofuran2×HCID 65578Oxalyl chlorideHCID 97834486123-11-7

Product 1

HCID 59976407HCID 59976407, compound

Procedure

A THF (15 ml) solution of oxalyl chloride (1.16 ml) was added dropwise to a THF (45 ml) solution of N-(9-fluorenylmethoxycarbonyl)-D-tryptophan (4.73 g) and DMF (0.1 ml) at 0° C. The reaction mixture was stirred at room temperature for 30 minutes, then concentrated. The residue was dissolved in ethyl acetate (30 ml), which was added dropwise to the mixture of an ethyl acetate (40 ml) solution of 3-(R,S)-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroquinoline (800 mg) and 20% aqueous sodium carbonate solution (40 ml), at 0° C. The reaction mixture was stirred at room temperature for one hour, and the organic layer was separated. The organic layer was washed with a saturated aqueous sodium chloride solution, then dried and concentrated. The residue was purified by alumina column chromatography (eluent: ethyl acetate/hexane=1:2 to 1:1), then concentrated. The residue was dissolved In methanol (60 ml). Piperidine (2 ml) was added to the mixture, which was stirred at room temperature for 12 hours. The reaction mixture was concentrated, and purified by alumina column chromatography (eluent: ethyl acetate/hexane=1:2 to ethyl acetate/methanol=20:1) to obtain the entitled compound (1.1 g) as an amorphous powder.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in ethyl acetate (30 ml)
  3. additionwhich was added dropwise to the mixture of an ethyl acetate (40 ml) solution of 3-(R,S)-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroquinoline (800 mg) and 20% aqueous sodium carbonate solution (40 ml), at 0° C
  4. stirringThe reaction mixture was stirred at room temperature for one hour
  5. customthe organic layer was separated
  6. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by alumina column chromatography (eluent: ethyl acetate/hexane=1:2 to 1:1)
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved In methanol (60 ml)
  12. additionPiperidine (2 ml) was added to the mixture, which
  13. stirringwas stirred at room temperature for 12 hours
  14. concentrationThe reaction mixture was concentrated
  15. custompurified by alumina column chromatography (eluent: ethyl acetate/hexane=1:2 to ethyl acetate/methanol=20:1)

Sources & evidence

ORD record
ord-48353a8086c8453c8fcf761010f953c0
Source dataset
uspto-grants-2001_12
Patent number
US06329389B1

Reaction notes

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