Lithium Hydroxide → (4-{4-[2-(3-Fluorophenylamino)-pyrimidin-5-yl]-phenyl}-cyclohexyl)-acetic acid

HRID 76027Notes

Reaction equation

C[O:2][C:3](=[O:31])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:18]=[N:19][C:20]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=4)=[N:21][CH:22]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[Li+].[OH-]>CN(C=O)C>[F:30][C:26]1[CH:25]=[C:24]([NH:23][C:20]2[N:19]=[CH:18][C:17]([C:14]3[CH:15]=[CH:16][C:11]([CH:8]4[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:31])=[O:2])[CH2:10][CH2:9]4)=[CH:12][CH:13]=3)=[CH:22][N:21]=2)[CH:29]=[CH:28][CH:27]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (4-{4-[2-(3-fluorophenylamino)-pyrimidin-5-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester (crude from above) in DMF (2.5 mL) is added LiOH (10% solution, 1 mL) and the reaction mixture is heated at 60° C. for 1.5 h. The mixture is then subjected to HPLC purification to give the title compound: 1H NMR (400 MHz, DMSO-d6) δ 1.09-1.15 (m, 1H) 1.50 (td, J=12.44, 9.98 Hz, 1H) 1.63 (d, J=5.31 Hz, 6H) 2.37 (d, J=7.58 Hz, 2H) 6.76 (td, J=8.21, 2.27 Hz, 1H) 7.28-7.39 (m, 4H) 7.52 (dd, J=8.34, 1.26 Hz, 1H) 7.65 (s, 1H) 7.63 (t, J=4.04 Hz, 2H) 7.87 (d, J=12.38 Hz, 1H) 8.84-8.86 (m, 2H) 9.99 (s, 1H); (M+H)+=406.2.

Workup

customThe mixture is then subjected to HPLC purification

Sources & evidence

ORD record: ord-4d3a8d87c2894a01abf4a777a2990f2a
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835451B2

Reaction notes

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