Methyl iodide → (2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-{3-[3-(4-methyl-piperazin-1-yl)-phenoxy]-propyl}-amine methanesulfonate

HRID 902704Notes

Reaction equation

HRID 902704 reaction equation
[Cl:1][C:2]1[C:39]([C:40]([F:43])([F:42])[F:41])=[CH:38][CH:37]=[CH:36][C:3]=1[CH2:4][N:5]([CH2:22][CH:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:11]=1.IC.[CH:46](N(C(C)C)CC)(C)C.[CH3:55][S:56]([OH:59])(=[O:58])=[O:57]>CN(C=O)C.C(Cl)Cl>[CH3:55][S:56]([OH:59])(=[O:58])=[O:57].[Cl:1][C:2]1[C:39]([C:40]([F:41])([F:43])[F:42])=[CH:38][CH:37]=[CH:36][C:3]=1[CH2:4][N:5]([CH2:22][CH:23]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N:16]2[CH2:17][CH2:18][N:19]([CH3:46])[CH2:20][CH2:21]2)[CH:11]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 6395Methanesulfonic AcidHCID 81531DiisopropylethylamineHCID 59701425(2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(3-piperazin-1-yl-phenoxy)-propyl]-amine

Product 1

HCID 86598297(2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-{3-[3-(4-methyl-piperazin-1-yl)-phenoxy]-propyl}-amine methanesulfonate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a stirring solution of (2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(3-piperazin-1-yl-phenoxy)-propyl]-amine (150 mg, 2.46 mmol) in anhydrous DMF (20 ml) was added iodomethane (16.8 uL, 2.71 mmol) and diisopropylethylamine (86 uL, 4.93 mmol). The resulting solution was heated at 50° C. for 4 hours and then concentrated. Purification by flash silica gel chromatography (silica gel 60, EM science; 3% MeOH and 0.5% NH2OH in CH2Cl2) afforded the N-methylated product. The amine was dissolved in CH2Cl2 and methansulfonic acid (2 equivalents) was added. The methylene chloride solution was concentrated and the resulting bis-methanesulfonate salt was dried under vacuum to yield the title compound as a solid, 56 mg (37%). MS(ES) m/e 622.4 (M+).

Workup

  1. concentrationconcentrated
  2. customPurification by flash silica gel chromatography (silica gel 60, EM science; 3% MeOH and 0.5% NH2OH in CH2Cl2)
  3. customafforded the N-methylated product
  4. concentrationThe methylene chloride solution was concentrated
  5. dry with materialthe resulting bis-methanesulfonate salt was dried under vacuum

Sources & evidence

ORD record
ord-c1d07e4af68540d3b719d0fd475642ca
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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