1,2-Dichloroethane → 2-[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2,4-dioxopiperidin-1-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

HRID 1866727ノート

反応式

HRID 1866727 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([OH:18])=O)[C:13](=[O:19])[C:12]([CH3:21])([CH3:20])[C:11](=[O:22])[CH2:10]2)[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>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([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:18])[C:13](=[O:19])[C:12]([CH3:20])([CH3:21])[C:11](=[O:22])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

参加物

6

反応物 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 53260812(R)-5-Amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2 回HCID 57974055[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2,4-dioxopiperidin-1-yl]acetic acid2 回

生成物 1

HCID 250207592-[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2,4-dioxopiperidin-1-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of [(6S)-6-(3,5-difluorophenyl)-3,3-dimethyl-2,4-dioxopiperidin-1-yl]acetic acid (156 mg, 0.501 mmol, described in Intermediate 22), (R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (145 mg, 0.577 mmol, described in Intermediate 9), HOBT (95 mg, 0.620 mmol), and EDC (123 mg, 0.642 mmol) in DMF (2 mL) was stirred at ambient temperature for 16 h. The reaction mixture was partitioned between H2O (60 mL) and EtOAc (100 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:CH3OH—100:0 to 90:10, to give the title compound. MS: m/z=545 (M+1). HRMS: m/z=545.2025; calculated m/z=545.1995 for C30H27F2N4O4.

後処理

  1. customThe reaction mixture was partitioned between H2O (60 mL) and EtOAc (100 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with a gradient of CH2Cl2

出典と根拠

ORDレコード
ord-b05411ca687245208731bfd131c5b120
出典データセット
uspto-grants-2009_12
特許番号
US07629338B2

反応ノート

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