2-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acid → Methyl 2-chloro-5-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate

HRID 219958ノート

反応式

HRID 219958 の反応式
[CH3:1][O:2][CH2:3][C:4]1[CH:9]=[C:8]([C:10]([OH:12])=O)[CH:7]=[CH:6][C:5]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].[NH2:20][C:21](=[N:34]O)[C:22]1[C:31]([F:32])=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([Cl:33])[CH:23]=1>>[Cl:33][C:24]1[CH:23]=[C:22]([C:21]2[N:20]=[C:10]([C:8]3[CH:7]=[CH:6][C:5]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[CH3:19])=[C:4]([CH2:3][O:2][CH3:1])[CH:9]=3)[O:12][N:34]=2)[C:31]([F:32])=[CH:30][C:25]=1[C:26]([O:28][CH3:29])=[O:27]

参加物

3

反応物 2

HCID 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 72307477Methyl 4-[amino(hydroxyimino)methyl]-2-chloro-5-fluorobenzoate

生成物 1

HCID 67528687Methyl 2-chloro-5-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate

実験手順

The title compound was prepared following procedure described for example 4, step 1, but starting from Intermediate 28 (230.67 mg; 0.90 mmol) and Intermediate 55 (184.97 mg; 0.75 mmol). The reaction mixture was filtered through a SPE NH2 column (2 g) and rinsed with ACN. The filtrate was passed through a SPE SCX column (2 g) and rinsed with ACN. After evaporation of the solvents, the crude product was purified by flash chromatography (c-hex/(DCM/EtOAc 1:1) gradient from 1:0 to 1:1). The white solid was washed with MeOH affording the title compound as a white powder. 1H NMR (CDCl3, 300 MHz) δ 8.44-8.43 (m, 1H), 8.35 (d, J=6.1 Hz, 1H), 8.18 (dd, J=7.9, 1.8 Hz, 1H), 7.77 (d, J=10.1 Hz, 1H), 7.35 (d, J=7.9 Hz, 1H), 7.32-7.24 (m, 3H), 7.13 (d, J=7.2 Hz, 1H), 4.27-4.18 (m, 2H), 3.99 (s, 3H), 3.34 (s, 3H), 2.08 (s, 3H). LC/MS (Method B): 467.1 (M+H)+. HPLC (Method A) Rt 6.09 min (Purity: 98.8%).

後処理

  1. filtrationThe reaction mixture was filtered through a SPE NH2 column (2 g)
  2. washrinsed with ACN
  3. washrinsed with ACN
  4. customAfter evaporation of the solvents
  5. customthe crude product was purified by flash chromatography (c-hex/(DCM/EtOAc 1:1) gradient from 1:0 to 1:1)
  6. washThe white solid was washed with MeOH affording the title compound as a white powder

出典と根拠

ORDレコード
ord-f70f428bc36e4815a91425c2de79aaed
出典データセット
uspto-grants-2012_06
特許番号
US08202865B2

反応ノート

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