5-Fluoroindole-2-carboxylic acid → HCID 67501170, compound

HRID 1920049Notes

Reaction equation

HRID 1920049 reaction equation
[N:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([C@@H:4]3[CH2:11][NH2:12])[CH2:2]1)[CH2:8]2.[F:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18]([C:23](O)=[O:24])=[CH:17]2.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1>[N:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([C@@H:4]3[CH2:11][NH:12][C:23]([C:18]3[NH:19][C:20]4[C:16]([CH:17]=3)=[CH:15][C:14]([F:13])=[CH:22][CH:21]=4)=[O:24])[CH2:2]1)[CH2:8]2

Participants

6

Reactant 4

HCID 18205-Fluoroindole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 189378471-Azatricyclo[3.3.1.13,7]decane-4-methanamine

Product 1

HCID 67501170HCID 67501170, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

The product of Example 2B (50 mg, 0.30 mmol) was dissolved in pyridine (5 mL). 5-Fluoroindole-2-carboxylic acid (65 mg, 0.36 mmol), 1-hydroxybenzotriazole (51 mg, 0.38 mmol), 4-di(methylamino)pyridine (9.2 mg, 0.08 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (86 mg, 0.45 mmol) were added to the reaction mixture. The reaction was stirred at 25° C. for 18 hours. The reaction mixture was filtered through a glass frit. The filtrate was concentrated in vacuo. The residue was purified by preparative HPLC on a Waters Nova-Pak® HR C18 6 μm 60 Å Prep-Pak® cartridge column (40 mm×100 mm) using a gradient of 10% to 100% acetonitrile in 10 mM aqueous ammonium acetate over 12 minutes at a flow rate of 70 mL/min to provide the free base of the title compound. The solid was dissolved in 10:1 ether/methanol (5 mL) and treated with fumaric acid (10 mg/mL solution in 10:1 ether/methanol). The precipitate was filtered and dried under vacuum to afford the title compound as a fumarate: 1H NMR (methanol-d4, 500 MHz) δ 1.95-2.02 (m, 2 H), 2.11-2.20 (m, 4 H), 2.20-2.28 (m, 2 H), 3.37-3.43 (m, 2 H), 3.51 (br s, 2 H), 3.62 (d, J=7.93 Hz, 2 H), 3.76-3.83 (m, 2 H), 6.69 (s, 2.6 H; C4H4O4), 7.00 (dt, J=9.15, 2.44 Hz, 1 H), 7.03 (s, 1 H), 7.26 (dd, J=9.46, 2.44 Hz, 1 H), 7.41 ppm (dd, J=8.85, 4.58 Hz, 1 H); MS (ESI) m/z 328 (M+H)+; Anal. Calcd. for C19H22FN3O.1.3C4H4O4.0.1NH4OAc: C, 60.3; H, 5.79; N, 8.93. Found: C, 59.98; H, 5.76; N, 9.19.

Workup

  1. filtrationThe reaction mixture was filtered through a glass frit
  2. concentrationThe filtrate was concentrated in vacuo
  3. customThe residue was purified by preparative HPLC on a Waters Nova-Pak® HR
  4. customover 12 minutes

Sources & evidence

ORD record
ord-edaa1fd4064844fa93cd0184ff808195
Source dataset
uspto-grants-2012_05
Patent number
US08168791B2

Reaction notes

Loading…