Acetone → HCID 58075523, compound

HRID 451196Notes

Reaction equation

HRID 451196 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:15]=[C:16]([N:29]4[CH2:37][CH2:36][C:31]5(OCC[O:32]5)[CH2:30]4)[C:17]4[CH2:22][CH2:21][CH:20]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[C:18]=4[N:19]=3)=[CH:9][C:8]=2[O:38][CH3:39])[CH:6]=1.Cl.CC(C)=O>C1COCC1>[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:15]=[C:16]([N:29]4[CH2:37][CH2:36][C:31](=[O:32])[CH2:30]4)[C:17]4[CH2:22][CH2:21][CH:20]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[C:18]=4[N:19]=3)=[CH:9][C:8]=2[O:38][CH3:39])[CH:6]=1

Participants

5

Reactant 3

HCID 180AcetoneHCID 313Hydrochloric Acid2×HCID 50912912HCID 50912912, compound

Product 1

HCID 58075523HCID 58075523, compoundYield 5.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

The mixture of N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-phenyl-4-(1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine (Example 205) (37 mg, 0.068 mmol) and HCl (272 μL, 0.272 mmol) in THF (339 μL) was heated at 60° C. overnight. Concentrated to remove THF and added Acetone (339 μL) and HCl (272 μL, 0.272 mmol) to the mixture. The mixture was heated at 60° C. for 6 h. The crude product was purified by Prep-HPLC (Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA. Column. PHENOMENEX LUNA 30×100 mm, S10, Flow rate: 40 ml/min, 35-100% B, 40 min) and then was 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% B, 35 min) to get 1-(2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)pyrrolidin-3-one (2.0 mg, 3.59 μmol, 5.29% yield).

Workup

  1. concentrationConcentrated
  2. customto remove THF
  3. temperatureThe mixture was heated at 60° C. for 6 h
  4. customThe crude product was purified by Prep-HPLC (Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA. Column. PHENOMENEX LUNA 30×100 mm, S10, Flow rate: 40 ml/min, 35-100% B, 40 min)
  5. customwas 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% B, 35 min)

Sources & evidence

ORD record
ord-2dac1706a4564d5f8dccef12f9d2f5f2
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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