Sodium Iodide → HCID 57632703, compound

HRID 2109801Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][C:12]([NH:15][C:16]3[CH:33]=[CH:32][C:19]([O:20][CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][CH:26]([C:29]([OH:31])=[O:30])[CH2:25][CH2:24]4)=[CH:18][CH:17]=3)=[N:13][CH:14]=2)=[CH:5][CH:4]=1.Cl[CH2:35][CH2:36]OC1C=CC(NC2N=CC(C3C=CC(OC)=CC=3)=CN=2)=CC=1.[I-].[Na+].N1CCC(C(OCC)=O)CC1>CN(C=O)C>[CH2:35]([O:30][C:29]([CH:26]1[CH2:25][CH2:24][N:23]([CH2:22][CH2:21][O:20][C:19]2[CH:32]=[CH:33][C:16]([NH:15][C:12]3[N:11]=[CH:10][C:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)=[CH:14][N:13]=3)=[CH:17][CH:18]=2)[CH2:28][CH2:27]1)=[O:31])[CH3:36]

Participants

Conditions

Temperature: 120 °C

Procedure

1-(2-{4-[5-(4-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenoxy}-ethyl)-piperidine-4-carboxylic acid can be synthesized by the following procedure. To a solution of [4-(2-chloro-ethoxy)-phenyl]-[5-(4-methoxy-phenyl)-pyrimidin-2-yl]-amine (0.042 mmol) (from Example 5d) in DMF (1 ml) is added sodium iodide (0.050 mmol) and ethyl isonipecotate (0.084 mmol). The reaction is heated at 120° C. for 12 h. Purification by HPLC (ACN gradient 10-90%) affords 1-(2-{4-[5-(4-methoxy-phenyl)-pyrimidin-2-ylamino]-phenoxy}-ethyl)-piperidine-4-carboxylic acid ethyl ester (50%). MS (m/z) (M+1)+ 477.0. This solid is suspended in a 3:2:1=THF:MeOH:H2O solution (0.5 mL) and 6N LiOH (0.126 mmol) and stirred at rt for 12 h. The reaction mixture is diluted with DMF and purified by HPLC (ACN gradient 10-90%) to afford 1-(2-{4-[5-(4-methoxy-phenyl)-pyrimidin-2-ylamino]-phenoxy}-ethyl)-piperidine-4-carboxylicacid. MS (m/z) (M+1)+ 449.2.

Workup

customPurification by HPLC (ACN gradient 10-90%)

Sources & evidence

ORD record: ord-c2e25ee50cd34629890cf17b44a38c03
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07514447B2

Reaction notes

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