Potassium Hydroxide → HCID 67338240, compound

HRID 82418Notes

Reaction equation

HRID 82418 reaction equation
[CH3:1][C:2]1([CH3:12])[C:10]2[C:9](=O)[NH:8][CH:7]=[N:6][C:5]=2[CH2:4][CH2:3]1.[OH-].[K+].[N:15]1([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1>C(#N)C.O=P(Cl)(Cl)Cl>[CH3:1][C:2]1([CH3:12])[C:10]2[C:9]([N:18]3[CH2:17][CH2:16][N:15]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][CH2:19]3)=[N:8][CH:7]=[N:6][C:5]=2[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 1362342305,5-dimethyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one

Product 1

HCID 67338240HCID 67338240, compoundYield 47.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 2,2-dimethyl-5-oxocyclopentanecarboxylate (3.426 g) and ammonium acetate (14.33 g) in EtOH (100 mL) was heated at 85° C. (bath) for 1 hour. The contents were concentrated. The residue was partitioned between water and DCM. The organic phase was separated. The aqueous solution was extracted with DCM. The combined DCM solutions were washed with water and dried (Na2SO4). Upon filtration and concentration, solid ethyl 2-amino-5,5-dimethylcyclopent-1-enecarboxylate (2.933 g) was yielded. The ethyl 2-amino-5,5-dimethylcyclopent-1-enecarboxylate was mixed with ammonium formate (5.054 g) and formamide (7 mL) and heated at 150° C. for 16 hours. The mixture was diluted with water and extracted with 5:1 DCM-IPA. The combined extracts were dried (Na2SO4) and concentrated to give 5,5-dimethyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one as a viscous oil (1.185 g). 5,5-Dimethyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one (1.063 g) was dissolved in acetonitrile (20 mL) with POCl3 (1.78 mL). The mixture was heated at 80° C. for 10 hours. The mixture was cooled to 0° C. 50% KOH (15.3 mL) was added dropwise. t-Butyl piperazine-1-carboxylate (3.615 g) was added. The mixture was heated at 80° C. for 24 hours. The contents were concentrated. Water was added. The mixture was extracted with DCM (2×) and dried (Na2SO4). The crude material was purified with flash chromatography to give tert-butyl 4-(5,5-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (1.021 g). 1H NMR (CDCl3, 400 MHz) δ (ppm): 8.57 (s, 1H), 3.56-3.54 (m, 4H), 3.37-3.34 (m, 4H), 2.90 (t, J=7.3 Hz, 2H), 1.89 (t, J=7.3 Hz), 3H) 1.48 (s, 9H), 1.40 (s, 6H). MS: 333.2 (M+1).

Workup

  1. temperatureThe mixture was cooled to 0° C
  2. temperatureThe mixture was heated at 80° C. for 24 hours
  3. concentrationThe contents were concentrated
  4. additionWater was added
  5. extractionThe mixture was extracted with DCM (2×)
  6. dry with materialdried (Na2SO4)
  7. customThe crude material was purified with flash chromatography

Sources & evidence

ORD record
ord-2bb95681b1014dbb80bc5303a62f9154
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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