Water → HCID 21057780, compound

HRID 719406Notes

Reaction equation

HRID 719406 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH2:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[N:5]=[C:4]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([F:25])[CH:18]=2)[N:3]=1.[NH2:26][CH2:27][CH:28]1[CH2:32][CH2:31][CH2:30][N:29]1[CH2:33][CH3:34].[OH-].[Na+].O>O1CCOCC1.CC(C)=O>[OH-:8].[NH4+:3].[CH:10]1([CH2:9][O:8][C:6]2[N:7]=[C:2]([NH:26][CH2:27][CH:28]3[CH2:32][CH2:31][CH2:30][N:29]3[CH2:33][CH3:34])[N:3]=[C:4]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([F:25])[CH:18]=3)[N:5]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 1172952-Aminomethyl-1-ethylpyrrolidineHCID 21897113HCID 21897113, compound

Product 2

HCID 14923Ammonium HydroxideHCID 21057780HCID 21057780, compoundYield 120.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a sample of 114 (0.3004 g, 0.82 mmol) dissolved in 1,4-dioxane (15 mL) was added a solution of 2-(aminomethyl)-1-ethylpyrrolidine (0.12 mL, 0.82 mmol) in acetone (1 mL) followed by the addition of NaOH (0.33 mL, 2.5 N, 0.82 mmol) and water (1 mL). The reaction mixture was allowed to stir at reflux for about 2 hours under nitrogen. The reaction mixture was extracted 3 times with dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was concentrated on the rotary evaporator and the resulting solid was dried overnight under vacuum. Column chromatography (silica gel, 93:6:1 dichloromethane:methanol:conc. ammonium hydroxide) yielded a light yellow solid, compound 116 (226 mg, 60%), mp 59° C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 10.5 min, 100% purity; 1H NMR (600 MHz, CDCl3, 55° C.) δ 7.65 (broad resonance, rotamers, 1H), 7.07 (br d, J=7.8 Hz, 1H), 6.90 (t, J=9 Hz, 1H) 6.84 (broad resonance, rotamers, 1H), 4.12 (s, 2H), 3.88 (S, 3H), 1.02 (s, 1H), 2.26 (apt sextet, J=6.6 Hz, 1H), 2.19 (q, J=9Hz, 1H), 1.16–1.92 (m, 10H), 1.57 (s, 2H), 1.17–1.32 (m, 3H), 1.05 -1.11 (m, 4H); MS (ESI): m/z 459 (M+H, 100), 363 (40.7), 223 (16.1), 202 (4.4), 138 (1.2).

Workup

  1. temperatureat reflux for about 2 hours under nitrogen
  2. extractionThe reaction mixture was extracted 3 times with dichloromethane
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over potassium carbonate
  5. concentrationThe sample was concentrated on the rotary evaporator
  6. customthe resulting solid was dried overnight under vacuum

Sources & evidence

ORD record
ord-be3a581ff3964f8cbb53f833ad4d0248
Source dataset
uspto-grants-2006_11
Patent number
US07132423B2

Reaction notes

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