Triphenylphosphine → (S)-2-methyl-7-morpholin-4-yl-1-[2-(4-morpholin-4-yl-phenyl)ethyl]-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one

HRID 72373Notes

Reaction equation

HRID 72373 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14]O)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:35][C@@:36]1([C:52]([F:55])([F:54])[F:53])[CH2:51][N:39]2[C:40](=[O:50])[CH:41]=[C:42]([N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)[N:43]=[C:38]2[NH:37]1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:35][C@@:36]1([C:52]([F:55])([F:53])[F:54])[CH2:51][N:39]2[C:40](=[O:50])[CH:41]=[C:42]([N:44]3[CH2:45][CH2:46][O:47][CH2:48][CH2:49]3)[N:43]=[C:38]2[N:37]1[CH2:14][CH2:13][C:10]1[CH:9]=[CH:8][C:7]([N:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 135928032-(4-Morpholinophenyl)ethanolHCID 136069602(2S)-2-methyl-7-morpholin-4-yl-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one

Product 1

HCID 50899523(S)-2-methyl-7-morpholin-4-yl-1-[2-(4-morpholin-4-yl-phenyl)ethyl]-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-oneYield 24.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

135 mg of 2-(4-morpholinophenyl)ethanol and 223 mg of polymer-supported triphenylphosphine (3 mmol/g) are added to a solution of 100 mg of (S)-2-methyl-7-morpholin-4-yl-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]-pyrimidin-5-one (Example 1j) in 5 ml of tetrahydrofuran. After stirring for five minutes at ambient temperature, 0.12 ml of diethyl azodicarboxylate is added. The resulting reaction mixture is then stirred overnight at ambient temperature. After filtration, the filtrate is evaporated under reduced pressure. The residue obtained is purified by silica column chromatography (eluent: dichloromethane/methanol 97/03), so as to give 40 mg of (S)-2-methyl-7-morpholin-4-yl-1-[2-(4-morpholin-4-yl-phenyl)ethyl]-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one, the characteristics of which are the following:

Workup

  1. customThe resulting reaction mixture
  2. stirringis then stirred overnight at ambient temperature
  3. filtrationAfter filtration
  4. customthe filtrate is evaporated under reduced pressure
  5. customThe residue obtained
  6. customis purified by silica column chromatography (eluent: dichloromethane/methanol 97/03)

Sources & evidence

ORD record
ord-bbe2e2b3a4dc4842b1e99f16bb1c5b98
Source dataset
uspto-grants-2014_09
Patent number
US08828997B2

Reaction notes

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