1,2-Dichloroethane → 2-[5-(3,5-Difluorophenyl)-3-ethyl-5-methyl-2,4-dioxoimidazolidin-1-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

HRID 1685392Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:9]2([CH3:22])[N:13]([CH2:14][C:15]([OH:17])=O)[C:12](=[O:18])[N:11]([CH2:19][CH3:20])[C:10]2=[O:21])[CH:5]=[C:6]([F:8])[CH:7]=1.[NH2:23][C:24]1[CH:25]=[C:26]2[C:39](=[CH:40][CH:41]=1)[CH2:38][C@:28]1([C:36]3[C:31](=[N:32][CH:33]=[CH:34][CH:35]=3)[NH:30][C:29]1=[O:37])[CH2:27]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[F:8][C:6]1[CH:5]=[C:4]([C:9]2([CH3:22])[N:13]([CH2:14][C:15]([NH:23][C:24]3[CH:25]=[C:26]4[C:39](=[CH:40][CH:41]=3)[CH2:38][C@:28]3([C:36]5[C:31](=[N:32][CH:33]=[CH:34][CH:35]=5)[NH:30][C:29]3=[O:37])[CH2:27]4)=[O:17])[C:12](=[O:18])[N:11]([CH2:19][CH3:20])[C:10]2=[O:21])[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of [5-(3,5-difluorophenyl)-5-methyl-2,4-dioxo-3-ethylimidazolidin-1-yl]acetic acid, isomer A (18 mg, 0.058 mmol, described in Intermediate 17), (R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (14 mg, 0.058 mmol, described in Intermediate 3), HOBT (13 mg, 0.086 mmol), EDC (17 mg, 0.086 mmol), and N,N-diisopropylethylamine (0.050 mL, 0.29 mmol) in DMF (0.5 mL) was stirred at 50° C. for 2 h. The reaction mixture was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. Lyophilization provided the title compound. MS: m/z=546 (M+1). HRMS: m/z=546.1944; calculated m/z=546.1948 for C29H26F2N5O4.

Workup

customThe reaction mixture was purified directly by HPLC
washeluting with a gradient of H2O

Sources & evidence

ORD record: ord-b6d01a9aff9c4ca1a296a8e53c36702a
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148390B2

Reaction notes

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