Dimethylacetamide → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-(trifluoromethyl)pyridin-2-ylcarbamate

HRID 340922

Reaction equation

[Cl:1][C:2]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:3]=1[CH2:4][NH:5][C:6](=[O:26])[N:7]([C@@H:9]([CH2:12][CH2:13][CH2:14][N:15]1[C:23](=[O:24])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]1=[O:25])[CH2:10][OH:11])[CH3:8].[F:32][C:33]([F:44])([F:43])[C:34]1[CH:35]=[CH:36][C:37](C(O)=O)=[N:38][CH:39]=1.C[C:46]([N:48](C)C)=[O:47].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>C1(C)C=CC=CC=1>[F:44][C:33]([F:32])([F:43])[C:34]1[CH:35]=[CH:36][C:37]([NH:48][C:46](=[O:47])[O:11][CH2:10][C@@H:9]([N:7]([CH3:8])[C:6]([NH:5][CH2:4][C:3]2[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:2]=2[Cl:1])=[O:26])[CH2:12][CH2:13][CH2:14][N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:25])=[N:38][CH:39]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of (S)-3-(2-chloro-3-fluorobenzyl)-1-(5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl)-1-methylurea (200 mg, 0.45 mmol), 5-(trifluoromethyl)picolinic acid (256 mg, 1.35 mmol) and DMA (0.3 mL, 1.35 mmol) in toluene (5 mL) was added DPPA (0.27 mL, 1.35 mmol). The mixture was heated to 100° C. for 2 h, and concentrated. The resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-(trifluoromethyl)pyridin-2-ylcarbamate (150 mg, 80%). LRMS (M+Na+) m/z 658.2.

Workup

concentrationconcentrated
customThe resulting residue was purified on RP-HPLC
additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record: ord-fd4dc44941c142bba2b2eab5d8b5f724
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895582B2

Linked notes

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