Diisopropylethylamine → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-chloropyridin-2-ylcarbamate

HRID 409819Notes

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].[Cl:32][C:33]1[CH:34]=[CH:35][C:36](C(O)=O)=[N:37][CH:38]=1.CC[N:44]([CH:48](C)C)C(C)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:58])=CC=1>C1(C)C=CC=CC=1>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([NH:44][C:48](=[O:58])[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:37][CH:38]=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 (480 mg, 1.07 mmol), 5-chloropicolinic acid (339 mg, 2.15 mmol), and DIEA (0.36 mL, 2.15 mmol) in toluene (10 mL) was added DPPA (0.46 mL, 2.15 mmol). The reaction mixture was heated to 100° C. for 2 h and concentrated to dryness. The residue was purified on RP-HPLC using a mixture of acetonitrile and water to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-chloropyridin-2-ylcarbamate (280 mg, 80% pure). LRMS (M+H+) m/z 602.2.

Workup

concentrationconcentrated to dryness
customThe residue was purified on RP-HPLC
additiona mixture of acetonitrile and water

Sources & evidence

ORD record: ord-d355a325016042d2938d4cc3a3350a86
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759374B2

Reaction notes

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