2-(Chloromethyl)pyrimidine → 2-{[4-(4-Phenyl-5-pyrimidin-4-yl-1H-imidazol-1-yl)piperidin-1-yl]methyl}pyrimidine

HRID 1896661Notes

Reaction equation

HRID 1896661 reaction equation
C1(C2N=CN(C3CCNCC3)C=2C2C=CN=CN=2)C=CC=CC=1.ClCC1N=CC=CN=1.F[C:33]1[CH:38]=[CH:37][C:36]([C:39]2[N:40]=[CH:41][N:42]([CH:51]3[CH2:56][CH2:55][N:54]([CH2:57][C:58]4[N:63]=[CH:62][CH:61]=[CH:60][N:59]=4)[CH2:53][CH2:52]3)[C:43]=2[C:44]2[CH:49]=[CH:48][N:47]=[C:46](N)[N:45]=2)=[CH:35][CH:34]=1>>[C:36]1([C:39]2[N:40]=[CH:41][N:42]([CH:51]3[CH2:56][CH2:55][N:54]([CH2:57][C:58]4[N:63]=[CH:62][CH:61]=[CH:60][N:59]=4)[CH2:53][CH2:52]3)[C:43]=2[C:44]2[CH:49]=[CH:48][N:47]=[CH:46][N:45]=2)[CH:35]=[CH:34][CH:33]=[CH:38][CH:37]=1

Participants

4

Reactant 3

HCID 128773712-(Chloromethyl)pyrimidineHCID 57461728HCID 57461728, compoundHCID 574617294-{4-(4-Fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}pyrimidin-2-amine

Product 1

HCID 582351342-{[4-(4-Phenyl-5-pyrimidin-4-yl-1H-imidazol-1-yl)piperidin-1-yl]methyl}pyrimidine

Procedure

The title product was prepared by reaction of 4-(4-phenyl-1-piperidin-4-yl-1H-imidazol-5-yl)pyrimidine (C23) with 2-(chloromethyl)pyrimidine according to the general procedure for the synthesis of 4-{4-(4-fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}pyrimidin-2-amine (3) in Example 3. In this case, after the reaction mixture was concentrated, the residue was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification was effected via silica gel chromatography (Eluant: 25% methanol in ethyl acetate) to provide the product as a white solid. Yield: 63 mg, 0.16 mmol, 62%. APCI m/z 398.1 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.11-2.20 (m, 4H), 2.23-2.32 (m, 2H), 3.13 (br d, J=12 Hz, 2H), 3.87 (s, 2H), 4.78 (tt, J=11, 4.5 Hz, 1H), 7.18 (dd, J=5.3, 1.5 Hz, 1H), 7.22 (t, J=4.9 Hz, 1H), 7.29-7.34 (m, 3H), 7.41-7.44 (m, 2H), 7.85 (s, 1H), 8.53 (br d, J=5.4 Hz, 1H), 8.76 (d, J=4.9 Hz, 2H), 9.29 (br d, J=1.5 Hz, 1H).

Workup

  1. concentrationIn this case, after the reaction mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification

Sources & evidence

ORD record
ord-d8830c50443c413499e0e9467b450504
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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