Heptane → 4-{4-(4-Fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}pyrimidin-2-amine

HRID 1896647Notes

Reaction equation

HRID 1896647 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[CH:11][N:12]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:13]=2[C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[N:15]=2)=[CH:5][CH:4]=1.Cl[CH2:28][C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CCCCCCC>CC1CCCO1.O>[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]=[CH:11][N:12]([CH:21]3[CH2:26][CH2:25][N:24]([CH2:28][C:29]4[N:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[CH2:23][CH2:22]3)[C:13]=2[C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[N:15]=2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 8900HeptaneHCID 10796Cesium carbonateHCID 128773712-(Chloromethyl)pyrimidineHCID 573998024-[4-(4-fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]pyrimidin-2-amine, hydrochloride salt

Product 1

HCID 574617294-{4-(4-Fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent

Procedure

A slurry of 4-[4-(4-fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]pyrimidin-2-amine, hydrochloride salt (C9, which can be prepared by the method of J. Sisko, U.S. Pat. No. 6,239,279 B1, May 29, 2001) (200 mg, 0.534 mmol), 2-(chloromethyl)pyrimidine (110 mg, 0.667 mmol) and cesium carbonate (365 mg, 1.12 mmol) in 2-methyltetrahydrofuran (3 mL) and water (1 mL) was heated overnight at 70° C. The resulting solution was cooled, and the organic layer was concentrated in vacuo. Addition of dichloromethane produced a solid; heptane (10 mL) was added, and the resulting mixture was stirred for 10 minutes. Filtration provided the title product as a solid. Yield: 205 mg, 0.476 mmol, 89%. APCI m/z 431.1 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.08-2.14 (m, 4H), 2.30-2.36 (m, 2H), 3.09 (br d, J=12 Hz, 2H), 3.84 (s, 2H), 4.62 (m, 1H), 6.40 (d, J=5.2 Hz, 1H), 7.07 (dd, J=8.8, 8.8 Hz, 2H), 7.39-7.43 (m, 3H), 8.04 (s, 1H), 8.13 (d, J=5.2 Hz, 1H), 8.80 (d, J=5.0 Hz, 2H).

Workup

  1. temperatureThe resulting solution was cooled
  2. concentrationthe organic layer was concentrated in vacuo
  3. additionAddition of dichloromethane
  4. customproduced a solid
  5. filtrationFiltration

Sources & evidence

ORD record
ord-87e8f61e74ef4ce6a9f687c1dc200466
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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