Lithium Hydroxide → 1-(3-(5 (4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzyl)piperidine-4-carboxylic acid

HRID 2067905Notes

Reaction equation

CS(O[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:13][C:14]2[N:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[CH:22][CH:21]=3)=[CH:16][N:15]=2)[CH:8]=1)(=O)=O.[NH:30]1[CH2:35][CH2:34][CH:33]([C:36]([O:38]C)=[O:37])[CH2:32][CH2:31]1.[Li+].[OH-]>CN(C=O)C.C1COCC1.CO.O>[F:29][CH:27]([F:28])[O:26][C:23]1[CH:24]=[CH:25][C:20]([C:17]2[CH:18]=[N:19][C:14]([NH:13][C:9]3[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=3)[CH2:6][N:30]3[CH2:31][CH2:32][CH:33]([C:36]([OH:38])=[O:37])[CH2:34][CH2:35]3)=[N:15][CH:16]=2)=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 3-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzyl methanesulfonate 37 (0.050 mmol) in anhydrous DMF (1 mL) is added methyl piperidine-4-carboxylate (0.10 mmol) and the solution is heated at 100° C. for 8 h. After the reaction is complete, the mixture is diluted with THF:MeOH:H2O (3:2:1, 5 mL). To the reaction mixture is added 6N LiOH (0.30 mmol). The reaction is stirred at rt for 1 h. Purification by preparative LC/MS affords 1-(3-(5 (4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzyl)piperidine-4-carboxylic acid E3. 1H NMR (400 MHz, d4-MeOH) δ 8.64 (s, 2H), 7.78 (d, J=8.8 Hz, 2H), 7.56 (d, J=8.8 Hz, 2H), 7.32 (d, J=8.8 Hz, 2H), 7.16 (d, J=8.8 Hz, 2H), 6.78 (t, J=74.0 Hz, 1H), 4.11 (s, 2H), 3.31 (m, 2H), 2.92 (m, 2H), 2.36 (m, 1H), 2.02 (m, 2H), 1.81 (m, 2H). MS (m/z) (M+1)+: 455.2.

Workup

customPurification by preparative LC/MS

Sources & evidence

ORD record: ord-57f568b1f5974f1f87a0962dd1162c6d
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Reaction notes

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