Ammonia → 2-Phenyl-1H-pyrrolo[2,3-f]isoquinoline-3-carboxylic acid amide

HRID 222111Notes

Reaction equation

HRID 222111 reaction equation
[C:1]1([C:7]2[NH:19][C:10]3=[C:11]4[C:16](=[CH:17][CH:18]=[C:9]3[C:8]=2[C:20]([OH:22])=O)[CH:15]=[N:14][CH:13]=[CH:12]4)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC[N:25](C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.N>C1COCC1.O.C(OC(=O)C)C>[C:1]1([C:7]2[NH:19][C:10]3=[C:11]4[C:16](=[CH:17][CH:18]=[C:9]3[C:8]=2[C:20]([NH2:25])=[O:22])[CH:15]=[N:14][CH:13]=[CH:12]4)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 687095872-phenyl-1H-pyrrolo[2,3-f]isoquinoline-3-carboxylic acid

Product 1

HCID 249899772-Phenyl-1H-pyrrolo[2,3-f]isoquinoline-3-carboxylic acid amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 2-phenyl-1H-pyrrolo[2,3-f]isoquinoline-3-carboxylic acid G2 (0.25 mmol) in THF (3 mL), DIEA (0.75 mmol) was added. The mixture was cooled to 0° C., EDCI hydrochloride (0.38 mmol) and HOBT.NH3 (0.38 mmol) were added and stirring at rt was maintained overnight. Ethylacetate and water were added, the layers were separated, the aqueous layer was extracted with ethylacetate and the combined organic layers were washed with water and with 1N NaOH. They were then dried (Na2SO4), filtered and evaporated. Treatment with a small amount of methanol caused precipitation of the product, which was filtered affording the title compound. The amide was suspended in methanol and treated with 4M HCl in dioxane until pH was 1. Solvent was removed, the residue was treated with diethylether and the resulting solid was filtered, washed with diethylether and dried, affording the hydrochloric salt of the title compound (43% yield). ESI (+) MS: m/z 288 (MH+). 1H NMR: 7.36 (bd, J=39.63, 2H), 7.50-7.55 (m, 1H), 7.56-7.62 (m, 2H), 7.82-7.87 (m, 2H), 7.96 (d, J=8.78, 1H), 8.24 (d, J=8.78, 1H), 8.69 (d, J=6.34, 1H), 8.77 (d, J=6.34, 1H), 9.59 (s, 1H), 13.07 (s, 1H).

Workup

  1. temperaturewas maintained overnight
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with ethylacetate
  4. washthe combined organic layers were washed with water and with 1N NaOH
  5. dry with materialThey were then dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customprecipitation of the product, which
  9. filtrationwas filtered

Sources & evidence

ORD record
ord-5477301b8652493dae798a7adffbb01f
Source dataset
uspto-grants-2012_06
Patent number
US08207180B2

Reaction notes

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