Potassium Carbonate → (S)-(2,4-Dichlorobenzyl)-[1-(4-trifluoromethyl-pyrimidin-2-yl)-pyrrolidin-3-yl]-amine

HRID 252137Notes

Reaction equation

HRID 252137 reaction equation
[Cl:1][C:2]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][NH:8][CH2:7]1.Cl[C:17]1[N:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][N:18]=1.C(=O)([O-])[O-].[K+].[K+]>>[Cl:1][C:2]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:17]2[N:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][N:18]=2)[CH2:7]1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 66569981(S)-N-(2,4-Dichlorobenzyl)pyrrolidin-3-amine

Product 1

HCID 59860357(S)-(2,4-Dichlorobenzyl)-[1-(4-trifluoromethyl-pyrimidin-2-yl)-pyrrolidin-3-yl]-amineYield 66%

Procedure

Stir a mixture of (S)-(2,4-dichlorobenzyl)-pyrrolidin-3-ylamine (266 mg, 1 mmol), 2-chloro-4-(trifluoromethyl)-pyrimidine (365 mg, 2 mmol) and polymer supported potassium carbonate (626 mg, 2 mmol) at 80° C. overnight. Filter away the polymer and pour the filtered reaction mixture onto a SCX-2 column. Elute with methanol and then elute with 2 M ammonia in methanol. Concentrate to give a residue and chromatograph on silica gel to give the title compound (258 mg, 66%). Prepare the hydrochloride salt essentially as described in EXAMPLE 1 to give the hydrochloride salt of the title compound. 1H NMR (400 MHz, MeOH-d4) δ 8.39 (2H, m), 7.71 (1H, d, J=8.56 Hz), 7.68 (1H, d, J=1.71 Hz), 7.51 (1H, dd, J=8.31, 1.96 Hz), 4.46-4.55 (2H, m), 4.19-4.26 (1H, m), 4.09-4.14 (1H, m), 3.89-3.98 (2H, m), 3.73 (1H, m), 2.63-2.70 (1H, m), 2.39-2.48 (1H, m), MS (ES): m/z=391 [M+].

Workup

  1. customat 80° C.
  2. customovernight
  3. filtrationFilter away the polymer
  4. additionpour
  5. customthe filtered reaction mixture onto a SCX-2 column
  6. washElute with methanol
  7. washelute with 2 M ammonia in methanol
  8. concentrationConcentrate
  9. customto give a residue and chromatograph on silica gel

Sources & evidence

ORD record
ord-cdd2992c4ce44b049f4b528da32393e6
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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