2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → HCID 51354603, compound

HRID 1994128Notes

Reaction equation

HRID 1994128 reaction equation
CN1C(=O)N(C)CCC1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:28])[CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)=[CH:13][C:12]=1[C:29]([F:32])([F:31])[F:30].Cl[C:34]1[CH:39]=[CH:38][N:37]=[C:36]([C:40]([NH:42][CH3:43])=[O:41])[CH:35]=1.CC([O-])(C)C.[K+]>O.CN(C=O)C>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:28])[CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][C:34]3[CH:39]=[CH:38][N:37]=[C:36]([C:40]([NH:42][CH3:43])=[O:41])[CH:35]=3)=[CH:23][CH:22]=2)=[CH:13][C:12]=1[C:29]([F:30])([F:31])[F:32]

Participants

7

Reactant 4

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 14768144-Chloro-N-methylpicolinamideHCID 23665647Potassium tert-butoxideHCID 51355180HCID 51355180, compound

Product 1

HCID 51354603HCID 51354603, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of DMPU (0.7 mL) and DMF (2.8 mL) was added N-[4-chloro-3-(trifluoromethyl)phenyl]-3-(4-hydroxyphenyl)propanamide (600 mg, 1.75 mmol) and 4-chloro-N-methylpyridine-2-carboxamide (prepared as described in Bankston, D. et al. Organic Process Research and Development 2002, 6, 777-781; 328 mg, 1.92 mmol). To this solution was added KOt-Bu (590 mg, 5.25 mmol). The reaction mixture was stirred at 100° C. for 18 h and then cooled to rt, diluted with water and extracted with EtOAc and DCM. The combined organic solutions were washed with water and brine, dried over Na2SO4, filtered and concentrated to give a brown oil. Purification by column chromatography provided 100 mg of a colorless solid. 1H NMR (300 MHz, CD3OD) δ: 10.11 (br s, 0.34H), 8.41 (d, J=5.6 Hz, 1H), 8.07 (br d, J=2.2 Hz, 1H), 7.74 (br dd, J1=8.7 Hz, J2=2.1 Hz, 1H), 7.48-7.51 (m, 2H), 7.36 (d, J=8.5 Hz, 1H), 7.05 (d, J=8.5 Hz, 2H), 6.98 (dd, J1=5.6 Hz, J2=2.5 Hz, 1H), 3.34 (s, 0.84H), 3.04 (t, J=7.5 Hz), 2.92 (s, 3H), and 2.71 (t, J=7.5 Hz).

Workup

  1. temperaturecooled to rt
  2. extractionextracted with EtOAc and DCM
  3. washThe combined organic solutions were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a brown oil
  8. customPurification by column chromatography

Sources & evidence

ORD record
ord-0f7a926b8ba24befa4d489c11f35f783
Source dataset
uspto-grants-2010_01
Patent number
US07652041B2

Reaction notes

Loading…