Hydrochloric Acid → HCID 178495952, compound

HRID 1257688Notes

Reaction equation

HRID 1257688 reaction equation
[N:1]1([C@H:13]2[CH2:17][CH2:16][C@H:15]([NH2:18])[CH2:14]2)[C:12]2[C:4](=[CH:5][N:6]=[C:7]3[C:11]=2[CH:10]=[CH:9][NH:8]3)[N:3]=[N:2]1.[CH3:19][O:20][CH2:21][CH2:22]Br.C(=O)([O-])[O-].[K+].[K+].[ClH:30].CO>C(Cl)Cl.CN(C=O)C>[ClH:30].[CH3:19][O:20][CH2:21][CH2:22][NH:18][C@H:15]1[CH2:16][CH2:17][C@H:13]([N:1]2[C:12]3[C:4](=[CH:5][N:6]=[C:7]4[C:11]=3[CH:10]=[CH:9][NH:8]4)[N:3]=[N:2]2)[CH2:14]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 178511584HCID 178511584, compound

Product 1

HCID 178495952HCID 178495952, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of racemic trans 3-(6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentylamine (95.0 mg, 392 μmol), 2-bromoethyl methyl ether (59.9 mg, 431 μmol), potassium carbonate (108 mg, 780 μmol) and DMF (2 mL) was heated to 135° C. for 15 minutes using microwave irradiation. The mixture was filtered, concentrated in vacuo and purified by column chromatography on silica gel (gradient: DCM to 10% [2M NH3 in methanol] in DCM) followed by reverse phase HPLC (5 to 50% acetonitrile in water, +0.1% NH4OH). The colourless residue was treated with 1.25 M HCl in methanol (2 eq) in DCM and concentrated to afford 17.6 mg of racemic trans (2-methoxy-ethyl)-[3-(6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-amine hydrochloride was isolated as a beige gum. LCMS (Method A, ESI): RT=1.92 min, m+H=301.3; 1H NMR (400 MHz, DMSO) δ: 12.35 (s, 1H), 8.99 (s, 1H), 7.60 (t, 1H), 7.00 (dd, 1H), 5.65 (m, 1H), 3.59 (m, 1H), 3.47 (t, 2H), 3.28 (s, 3H), 2.83 (t, 2H), 2.47 (m, 2H, partially obscured by DMSO), 2.29-2.17 (m, 3H), 1.72 (m, 1H).

Workup

  1. custommicrowave irradiation
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated in vacuo
  4. custompurified by column chromatography on silica gel (gradient: DCM to 10% [2M NH3 in methanol] in DCM)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-0cf044bfa46e4f548c6c14bcad341c7d
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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