Chloride → HCID 90338506, compound

HRID 1508710Notes

Reaction equation

HRID 1508710 reaction equation
Cl[C:2]1[C:3]2[CH2:17][CH2:16][CH2:15][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)[N:7]=1.CN1C(=O)CCC1.[CH3:25][C:26]1[CH:34]=[CH:33][C:29]([CH2:30][Mg]Cl)=[CH:28][CH:27]=1.[Cl-]>C1COCC1>[Cl:14][C:10]1[CH:9]=[C:8]([C:6]2[N:7]=[C:2]([CH2:25][C:26]3[CH:34]=[CH:33][C:29]([CH3:30])=[CH:28][CH:27]=3)[C:3]3[CH2:17][CH2:16][CH2:15][C:4]=3[N:5]=2)[CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 312ChlorideHCID 13387N-methyl-2-pyrrolidoneHCID 218826774-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidineHCID 178425359HCID 178425359, compound

Product 1

HCID 90338506HCID 90338506, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 25-mL round bottom flask, with stirrer bar, was charged with 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (318 mg, 1.20 mol, 1.0 eq.) and Fe(acac)3 (6.6 mg, 19 mol, 0.05 eq.), NMP (0.4 mL) and THF (4.0 mL). The mixture was cooled to 0° C. under nitrogen. A solution of 4-methylbenzylmagnesium chloride (0.83 mL, 0.5M in THF, 0.41 mmol, 1.1 eq.) was added dropwise over 2 minutes. The resulting mixture was stirred 0° C. for 1.5 hr until the starting chloride was consumed. The reaction was quenched with a 9:1 sat. NH4Cl/conc. NH4OH solution (10 mL) then diluted with ethyl acetate (75 mL). The organic layer was washed with sat. sodium chloride (3×5 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue (175 mg) was purified by chromatography on silica gel using dichloromethane as the eluent, to afford 2-(3-chlorophenyl)-4-(4-methylbenzyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (65 mg, 52% yield) as a white solid. MW=334.84. 1H NMR (DMSO-d6, 500 MHz) δ 8.35-8.30 (m, 2H), 7.58-7.51 (m, 2H), 7.20 (d, J=8.0 Hz, 2H), 7.11 (d, J=8.0 Hz, 2H), 4.07 (s, 2H), 2.97 (t, J=7.5 Hz, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.25 (s, 3H), 2.06 (quintet, J=7.5 Hz, 2H).

Workup

  1. customwas consumed
  2. customThe reaction was quenched with a 9:1 sat. NH4Cl/conc
  3. additionNH4OH solution (10 mL) then diluted with ethyl acetate (75 mL)
  4. washThe organic layer was washed with sat. sodium chloride (3×5 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue (175 mg) was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-c2069886c00f4b85bc935d9343133dd0
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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