Sodium Iodide → {4-[2-(4-{2-[4-(Tetrahydro-furan-2-carbonyl)-piperazin-1-yl]-ethoxy}-benzyl)-pyrimidin-5-yl]-benzylamino}-acetic acid tert-butyl ester

HRID 230071

Reaction equation

HRID 230071 reaction equation
[C:1]([O:5][C:6](=[O:33])[CH2:7][NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[N:18][C:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31]Cl)=[CH:25][CH:24]=3)=[N:20][CH:21]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[I-].[Na+].[O:36]1[CH2:40][CH2:39][CH2:38][CH:37]1[C:41]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)=[O:42]>CN(C=O)C>[C:1]([O:5][C:6](=[O:33])[CH2:7][NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[N:18][C:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:46]4[CH2:47][CH2:48][N:43]([C:41]([CH:37]5[CH2:38][CH2:39][CH2:40][O:36]5)=[O:42])[CH2:44][CH2:45]4)=[CH:25][CH:24]=3)=[N:20][CH:21]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 27346411-(Tetrahydro-2-furoyl)piperazineHCID 67140525(4-{2-[4-(2-Chloro-ethoxy)-benzyl]-pyrimidin-5-yl}-benzylamino)-acetic acid tert-butyl ester

Product 1

HCID 67140856{4-[2-(4-{2-[4-(Tetrahydro-furan-2-carbonyl)-piperazin-1-yl]-ethoxy}-benzyl)-pyrimidin-5-yl]-benzylamino}-acetic acid tert-butyl esterYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

{4-[2-(4-{{2-[4-(Tetrahydro-furan-2-carbonyl)-piperazin-1-yl]-ethoxy}-benzyl)-pyrimidin-5-yl]-benzylamino]-acetic acid tert-butyl ester can be synthesized by the following procedure. To a solution of (4-{2-[4-(2-chloro-ethoxy)-benzyl]-pyrimidin-5-yl}-benzylamino)-acetic acid tert-butyl ester (0.032 mmol) (from Example 5y) in anhydrous DMF is added sodium iodide (0.0384 mmol) and 1-(tetrahydro-2-furoyl)-piperazine (0.16 mmol). The reaction mixture is heated at 90° C. for 8 h. Purification by preparative LCMS (ACN gradient 10-90%) affords {4-[2-(4-{2-[4-(tetrahydro-furan-2-carbonyl)-piperazin-1-yl]-ethoxy}-benzyl)-pyrimidin-5-yl]-benzylamino}-acetic acid tert-butyl ester (51%). 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=8.0 Hz, 2H), 7.62 (d, J=8.8 Hz, 1H), 7.58 (d, J=8.8 Hz, 2H), 7.51 (d, J=8.0 Hz, 2H), 7.46 (d, J=7.2 Hz, 1H), 6.85 (d, J=9.2 Hz, 2H), 4.3 (m, 4H), 3.85 (m, 4H), 3.76 (m, 3H), 3.52 (m, 4H), 2.35 (m, 4H), 2.0 (m, 4H), 1.48 (s, 9H). MS (m/z) (M+1)+ 617.2.

Workup

  1. customPurification by preparative LCMS (ACN gradient 10-90%)

Sources & evidence

ORD record
ord-4ddd8748a6934be594f121540acbd91a
Source dataset
uspto-grants-2009_07
Patent number
US07563894B2

Linked notes

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