Hydrochloric Acid → (S)-3-Phenyl-2-(3-{2-[6-(tetrahydro-pyran-2-yloxycarbamoyl)-hexyl-carbamoyl]-1H-indol-5-yl}-propionylamino)-propionic acid cyclopentyl ester

HRID 548258Notes

Reaction equation

HRID 548258 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([C:20]1[NH:21][C:22]2[C:27]([CH:28]=1)=[CH:26][C:25]([CH2:29][CH2:30]C(O)=O)=[CH:24][CH:23]=2)=[O:19])=[O:10].CCN=C=N[CH2:39][CH2:40][CH2:41][N:42]([CH3:44])C.Cl.Cl.C(N(CC)CC)C.C1[CH:55]=[CH:56][C:57]2N(O)N=N[C:58]=2[CH:59]=1.[CH:64]1([O:69][C:70](=[O:80])[C@H](CC2C=CC=CC=2)N)[CH2:68][CH2:67][CH2:66][CH2:65]1.CC1C=CC(S(O)(=O)=[O:89])=CC=1>C(Cl)Cl.CN(C=O)C.C(Cl)Cl>[CH:64]1([O:69][C:70](=[O:80])[C@@H:41]([NH:42][C:44](=[O:89])[CH2:30][CH2:29][C:25]2[CH:26]=[C:27]3[C:22](=[CH:23][CH:24]=2)[NH:21][C:20]([C:18](=[O:19])[NH:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C:9](=[O:10])[NH:8][O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)=[CH:28]3)[CH2:40][C:39]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:68][CH2:67][CH2:66][CH2:65]1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 53840847Cyclopentyl (2S)-2-amino-3-phenylpropanoateHCID 579716513-{2-[6-(Tetrahydro-pyran-2-yloxycarbamoyl)-hexylcarbamoyl]-1H-indol-5-yl}-propionic acid

Product 1

HCID 57971647(S)-3-Phenyl-2-(3-{2-[6-(tetrahydro-pyran-2-yloxycarbamoyl)-hexyl-carbamoyl]-1H-indol-5-yl}-propionylamino)-propionic acid cyclopentyl esterYield 95%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

3-{2-[6-(Tetrahydro-pyran-2-yloxycarbamoyl)-hexylcarbamoyl]-1H-indol-5-yl}-propionic acid (0.357 g, 0.78 mmol) was dissolved in DCM/DMF (20 ml/20 ml). EDCl.HCl (0.163 mg, 0.86 mmol), triethylamine (0.24 ml, 1.7 mmol), HOBt (0.116 mg, 0.88 mmol) and L-phenylalanine cyclopentyl ester.TsOH salt (0.346 mg, 0.88 mmol) were added and the reaction mixture stirred for 16 h at room temperature under nitrogen. The solvent volume was reduced (˜10 ml), DCM was added and the organic layer washed with water (×3). The organic layer was dried (Na2SO4) and the solvent removed to give the required product (500 mg, 95% yield) which was used without further purification. LCMS purity 77%, m/z 675 [M++H]+

Workup

  1. additionwas added
  2. washthe organic layer washed with water (×3)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. customthe solvent removed

Sources & evidence

ORD record
ord-d8a6afc2677447db9011ad0b38b703a4
Source dataset
uspto-grants-2011_05
Patent number
US07939666B2

Reaction notes

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