Hydrochloric Acid → HCID 9959108, compound

HRID 489104Notes

Reaction equation

HRID 489104 reaction equation
[NH2:1][C:2](=[O:30])[C:3]([C:5]1[C:13]2[C:8](=[C:9]3[CH2:21][CH2:20][CH2:19][C:10]3=[CH:11][C:12]=2[O:14][CH2:15][C:16]([OH:18])=O)[N:7]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:6]=1[CH3:29])=[O:4].C(N(C(C)C)CC)(C)C.[C:40]1([S:46]([NH2:49])(=[O:48])=[O:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.Cl.CN(C)CCCN=C=NCC.Cl>C(Cl)Cl.C(OCC)(=O)C>[C:40]1([S:46]([NH:49][C:16](=[O:18])[CH2:15][O:14][C:12]2[CH:11]=[C:10]3[C:9]([CH2:21][CH2:20][CH2:19]3)=[C:8]3[C:13]=2[C:5]([C:3](=[O:4])[C:2]([NH2:1])=[O:30])=[C:6]([CH3:29])[N:7]3[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)(=[O:48])=[O:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7370Benzenesulfonamide2×HCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 10223013HCID 10223013, compound

Product 1

HCID 9959108HCID 9959108, compoundYield 9.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[[3-(2-amino-1,2-dioxoethyl)-2-methyl-1-benzyl-1,6,7,8-tetrahydrocyclopent[g]indol-4-yl]oxy]acetic acid (83 mg, 0.20 mmol) in methylene chloride (3 mL) was added diisopropylethylamine (0.1 mL, 0.6 mmol), 4-N,N-dimethylaminopyridine (24 mg, 0.20 mmol), benzenesulfonamide (31 mg, 0.20 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (58 mg, 0.37 mmol). The mixture was stirred at room temperature for 18 h. Additional portions of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (29 mg), diisopropylethylamine (51 μL), and benzenesulfonamide (16 mg) were added and the resulting mixture stirred for 5 h. The mixture was poured into 1 N hydrochloric acid and extracted three times with methylene chloride. The combined methylene chloride extracts were washed once with water, once with saturated aqueous sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo. Chromatography (silica gel, 7% methanol/93% chloroform) of the residue provided a solid that was slurried in hot ethyl acetate. Collection of the resulting solid via vacuum filtration provided 10 mg (9%) of the title compound as a yellow solid. 1H NMR (CDCl3) δ 10.95 (s, 1H), 7.91 (d, J=7.7 Hz, 2H), 7.55 (t, J=7.4 Hz, 1H), 7.38 (t, J=7.7 Hz, 2H), 7.20-7.35 (m, 4H), 6.91 (d, J=7.0 Hz, 2H), 6.21 (s, 1H), 5.84 (bs, 1H), 5.48 (s, 2H), 4.55 (s, 2H), 2.98 (t, J=7.3 Hz, 2H), 2.71 (t, J=7.7 Hz, 2H), 2.48 (s, 3H), 2.01 (quintet, J=7.7 Hz, 2H).

Workup

  1. stirringthe resulting mixture stirred for 5 h
  2. extractionextracted three times with methylene chloride
  3. washThe combined methylene chloride extracts were washed once with water, once with saturated aqueous sodium chloride solution
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customChromatography (silica gel, 7% methanol/93% chloroform) of the residue provided a solid
  8. customCollection of the resulting solid
  9. filtrationvia vacuum filtration

Sources & evidence

ORD record
ord-a0cb1ca9b4aa467c8e01a81805556629
Source dataset
uspto-grants-2005_12
Patent number
US06974831B2

Reaction notes

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