4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-butyl]-amide → 4,6-Dimethylpyrimidine-5-carboxylic acid [3-(4-oxo-piperidin-1-yl)-butyl]-amide

HRID 1711125Notes

Reaction equation

HRID 1711125 reaction equation
O1[C:5]2([CH2:10][CH2:9][N:8]([CH:11]([CH3:25])[CH2:12][CH2:13][NH:14][C:15]([C:17]3[C:18]([CH3:24])=[N:19][CH:20]=[N:21][C:22]=3[CH3:23])=[O:16])[CH2:7][CH2:6]2)[O:4]CC1>CC(C)=O.Cl>[O:4]=[C:5]1[CH2:10][CH2:9][N:8]([CH:11]([CH3:25])[CH2:12][CH2:13][NH:14][C:15]([C:17]2[C:22]([CH3:23])=[N:21][CH:20]=[N:19][C:18]=2[CH3:24])=[O:16])[CH2:7][CH2:6]1

Participants

4

Reactant 1

HCID 866295134,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-butyl]-amide

Product 1

HCID 594582434,6-Dimethylpyrimidine-5-carboxylic acid [3-(4-oxo-piperidin-1-yl)-butyl]-amideYield 23%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 313Hydrochloric AcidSolvent

Procedure

A solution of 4,6-dimethyl-pyrimidine-5-carboxylic acid [3-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-butyl]-amide (3.11 g, 8.95 mmol) in acetone (10 ml) and HCl 6N (aq, 8 ml) was refluxed for 18 h. The reaction mixture was quenched with NaOH (aq, 15%) to pH 7-8. The organic material was extracted with CH2Cl2 and the organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (10% MeOH in CH2Cl2; 2.5% NH4OH) to afford 4,6-dimethyl-pyrimidine-5-carboxylic acid [3-(4-oxo-piperidin-1-yl)-butyl]-amide (589 mg, 23%). 1H NMR (CDCl3) δ 1.04 (d, 3H, J=6.6 Hz), 1.64-1.72 (m, 1H), 1.81-1.91 (m, 1H), 2.15-2.30 (m, 4H), 2.52 (s, 6H), 2.62-2.72 (m, 2H), 2.84-2.98 (m, 3H), 3.47-3.62 (m, 1H), 3.69-3.77 (m, 1H), 6.94 (br s, 1H), 8.93 (s, 1H).

Workup

  1. customThe reaction mixture was quenched with NaOH (aq, 15%) to pH 7-8
  2. extractionThe organic material was extracted with CH2Cl2
  3. dry with materialthe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (10% MeOH in CH2Cl2; 2.5% NH4OH)

Sources & evidence

ORD record
ord-eb51247c6cfe460bb923c8893b5473ad
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

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