Dimethylformamide → HCID 131723017, compound

HRID 2269763Notes

Reaction equation

HRID 2269763 reaction equation
[CH2:1]1[CH2:5]O[CH2:3][CH2:2]1.[C:6]([Cl:11])(=O)[C:7](Cl)=O.[CH:12]1[C:24]2[CH:23]([CH2:25][O:26][C:27]([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:28])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]=2[CH:15]=[CH:14][CH:13]=1.[CH3:44][N:45]([CH:47]=O)[CH3:46]>>[Cl:11][C:6]1[CH:7]=[C:5]2[C:1]([CH2:32][CH:31]([CH2:47][N:45]([CH3:46])[CH3:44])[CH2:30][N:29]2[C:41](=[O:43])[C@H:30]([NH:29][C:27]([O:26][CH2:25][CH:23]2[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16]3[C:24]2=[CH:12][CH:13]=[CH:14][CH:15]=3)=[O:28])[CH2:31][C:32]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[NH:34][CH:33]=2)=[CH:2][CH:3]=1

Participants

5

Reactant 4

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

Product 1

HCID 131723017HCID 131723017, compound

Conditions

Temperature
0 °C

Procedure

A THF (10 ml) solution of oxalyl chloride (1.6 ml) was added dropwise to a THF (50 ml) solution of N-(9-fluorenylmethoxycarbonyl)-D-tryptophan (6.444 g) and DMF (0.14 ml) at 0° C. The reaction mixture was stirred at 0° C. for one hour, then concentrated. An ethyl acetate (15 ml) solution of the residue was added dropwise to the mixture of an ethyl acetate (30 ml) solution of 7-chloro-3-(N, N-dimethylamino )methyl-1,2,3, 4-tetrahydroquinoline (1.128 g) and a saturated aqueous sodium bicarbonate solution (25 ml) at 0° C. The reaction mixture was stirred at room temperature f or 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: hexane/ethyl acetate=1/1) to obtain 7-chloro-3-(R,S)-(N,N-dimethylamino)methyl-1-[2-(R)-(9-fluorenylmethoxy)carbonylamino-3-(indol-3-yl)propanoyl]-1,2,3,4-tetrahydroquinoline (107.4 g). Piperidine (1.4 ml) was added to a methanol (30 ml) solution of this compound at room temperature. The reaction mixture was stirred at room temperature for 15 hours, then concentrated. The residue was purified by alumina column chromatography (eluent: ethyl acetate/methanol=10/1) to obtain the entitled compound (1.012 g).

Workup

  1. concentrationconcentrated
  2. additionAn ethyl acetate (15 ml) solution of the residue was added dropwise to the mixture of an ethyl acetate (30 ml) solution of 7-chloro-3-(N, N-dimethylamino )methyl-1,2,3, 4-tetrahydroquinoline (1.128 g)
  3. customat 0° C
  4. stirringThe reaction mixture was stirred at room temperature f or 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: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-5fd54582608b480d87246890db50d927
Source dataset
uspto-grants-2001_12
Patent number
US06329389B1

Reaction notes

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