Ethylene Glycol → HCID 58075733, compound

HRID 2370109Notes

Reaction equation

HRID 2370109 reaction equation
[CH2:1]([OH:4])[CH2:2][OH:3].[Cl:5][C:6]1[N:7]=[C:8]([N:21]2[CH2:25][CH2:24][C:23](=O)[CH2:22]2)[C:9]2[CH2:14][CH2:13][CH:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:10]=2[N:11]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1>[Cl:5][C:6]1[N:7]=[C:8]([N:21]2[CH2:25][CH2:24][C:23]3([O:4][CH2:1][CH2:2][O:3]3)[CH2:22]2)[C:9]2[CH2:14][CH2:13][CH:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:10]=2[N:11]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 58075532HCID 58075532, compound

Product 1

HCID 58075733HCID 58075733, compoundYield 15.94%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

The mixture of ethylene glycol (46.9 μL, 0.841 mmol), 1-(2-chloro-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)pyrrolidin-3-one (Intermediate Gn) (132 mg, 0.421 mmol) and 4-methylbenzenesulfonic acid, H2O (8.00 mg, 0.042 mmol) in Benzene (1169 μL) was heated at reflux for 24 h in a Dean-stark apparatus. The resulting mixture was concentrated and purified by Prep-HPLC (Column: PHENOMENEX LUNA C18 30×100 mm, Solvent A=10 mM Ammonium Acetate in 95:5 H2O/ACN, Solvent B=10 mM Ammonium Acetate in 5:95 H2O/ACN. Flow rate: 40 ml/min, 30-100, 20 min) to get 7-(2-chloro-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-1,4-dioxa-7-azaspiro[4.4]nonane (24 mg, 0.067 mmol, 15.94% yield). LC-MS (M+H)+=358.1. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.31 (2 H, t, J=7.63 Hz), 7.20-7.25 (1 H, m), 7.15 (2 H, d, J=7.63 Hz), 4.21 (1 H, dd, J=9.16, 6.10 Hz), 4.01-4.06 (4 H, m), 3.89-3.97 (2 H, m), 3.77-3.84 (2 H, m), 3.26 (1 H, ddd, J=15.03, 8.62, 5.95 Hz), 3.13 (1 H, ddd, J=14.95, 8.85, 5.80 Hz), 2.53-2.63 (1 H, m), 2.17 (2 H, t, J=7.17 Hz), 2.03-2.12 (1 H, m).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 24 h in a Dean-stark apparatus
  3. concentrationThe resulting mixture was concentrated
  4. custompurified by Prep-HPLC (Column: PHENOMENEX LUNA C18 30×100 mm, Solvent A=10 mM Ammonium Acetate in 95:5 H2O/ACN, Solvent B=10 mM Ammonium Acetate in 5:95 H2O/ACN. Flow rate: 40 ml/min, 30-100, 20 min)

Sources & evidence

ORD record
ord-5ba64a3a3a454d8b9ea16cf78febe276
Source dataset
uspto-grants-2014_04
Patent number
US08710061B2

Reaction notes

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