Trifluoroacetic acid → HCID 90338528, compound

HRID 1508794Notes

Reaction equation

HRID 1508794 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[NH:9][CH:10]=[CH:11][CH:12]=2)[N:5]=[C:4]2[CH2:13][CH2:14][CH2:15][C:3]=12.[NH2:16][C:17]1[CH:25]=[CH:24][C:20]([CH2:21][CH2:22][OH:23])=[CH:19][CH:18]=1.O.C(#N)C.C(O)(C(F)(F)F)=O>Cl.CN1C(=O)CCC1.C(=O)(O)[O-].[Na+].ClCCl>[NH:9]1[CH:10]=[CH:11][CH:12]=[C:8]1[C:6]1[N:5]=[C:4]2[CH2:13][CH2:14][CH2:15][C:3]2=[C:2]([NH:16][C:17]2[CH:25]=[CH:24][C:20]([CH2:21][CH2:22][OH:23])=[CH:19][CH:18]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 669044-Aminophenethyl alcoholHCID 18373917Acetonitrile--water (1/1)HCID 90111257HCID 90111257, compound

Product 1

HCID 90338528HCID 90338528, compoundYield 35%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidCatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

A 10-mL microwave vial was charged with 4-chloro-2-(1H-pyrrol-2-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine (0.077 g, 0.35 mmol), 4-aminophenethyl alcohol (0.072 g, 0.53 mmol) and cone. HCl (1 drop) in NMP (2.5 mL). The resulting mixture was heated at 140° C. under microwave irradiation for 1.5 h. After this time, the reaction mixture was cooled, diluted with saturated aqueous sodium bicarbonate (15 mL) affording a brown solid. The solid was isolated by filtration and chromatography on silica using dichloromethane/(90:10:0.25 dichloromethane/methanol. conc. NH4OH) (10:0 to 0:10) as eluent followed by preparative HPLC (water/acetonitrile with 0.05% TFA) to afford 2-(4-((2-(1H-pyrrol-2-yl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)ethanol (0.039 g, 35%) as a light brown. MW=319.40. 1H NMR (DMSO-d6, 500 MHz) δ 11.16 (br s, 1H), 7.90 (br s, 1H), 7.22-7.18 (m, 2H), 7.15-7.11 (m, 2H), 7.01 (s, 1H), 6.73 (s, 1H), 6.38 (s, 1H), 6.06-6.01 (m, 1H), 4.62 (t, J=5.0 Hz, 1H), 3.65-3.58 (m, 2H), 2.86 (t, J=7.5 Hz, 2H), 2.78 (t, J=7.5 Hz, 2H), 2.71 (t, J=7.0 Hz, 2H), 2.05 (quin, J=7.5 Hz, 2H); ESI MS m/z 320 [M+H]+. Treatment with 1.25 M HCl in methanol (0.25 mL, 0.32 mmol) afforded the title compound (0.034 g, 92%) as a light brown solid. MW=355.86. M.p. 138-140° C. 1H NMR (DMSO-d6, 500 MHz) δ 13.50 (br s, 1H), 12.08 (br s, 1H), 9.44 (br s, 1H), 7.36-7.32 (m, 2H), 7.30-7.26 (m, 2H), 7.12-7.09 (m, 1H), 7.06 (s, 2H), 6.28-6.25 (m, 1H), 4.68 (br s, 1H), 3.66 (t, J=7.0 Hz, 2H), 3.11 (t, J=7.5 Hz, 2H), 2.87 (t, J=7.5 Hz, 2H), 2.78 (t, J=7.0 Hz, 2H), 2.20 (quin, J=7.5 Hz, 2H); ESI MS: ES m/z 320 [M+H]+.

Workup

  1. temperatureAfter this time, the reaction mixture was cooled
  2. customaffording a brown solid
  3. customThe solid was isolated by filtration and chromatography on silica

Sources & evidence

ORD record
ord-38d50591a2e74d3ea9c2079579efe656
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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