2-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acid → tert-butyl N-(2-fluoro-5-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)-N-methyl-beta-alaninate

HRID 219980Notes

Reaction equation

HRID 219980 reaction equation
[NH2:1][C:2](=[N:22][OH:23])[C:3]1[CH:4]=[CH:5][C:6]([F:21])=[C:7]([CH:20]=1)[CH2:8][N:9]([CH3:19])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[CH3:24][O:25][CH2:26][C:27]1[CH:32]=[C:31]([C:33](O)=O)[CH:30]=[CH:29][C:28]=1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[CH3:42]>>[F:21][C:6]1[CH:5]=[CH:4][C:3]([C:2]2[N:1]=[C:33]([C:31]3[CH:30]=[CH:29][C:28]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=4[CH3:42])=[C:27]([CH2:26][O:25][CH3:24])[CH:32]=3)[O:23][N:22]=2)=[CH:20][C:7]=1[CH2:8][N:9]([CH3:19])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

3

Reactant 2

HCID 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 72307493tert-butyl N-{5-[amino(hydroxyimino)methyl]-2-fluorobenzyl}-N-methyl-beta-alaninate

Product 1

HCID 67529270tert-butyl N-(2-fluoro-5-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)-N-methyl-beta-alaninate

Procedure

The title compound was prepared following procedure described for example 4, step 1, but starting from Intermediate 63 (268.44 mg; 0.83 mmol) and Intermediate 28 (192.22 mg; 0.75 mmol). The reaction mixture was filtered through a SPE NH2 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), affording the title compound as a colorless oil. 1H NMR (CDCl3) δ 8.42 (d, J=1.4 Hz, 1H), 8.25-8.22 (m, 1H), 8.17 (dd, J=7.8, 1.9 Hz, 1H), 8.12-8.07 (m, 1H), 7.36-7.23 (m, 4H), 7.20-7.12 (m, 2H), 4.23 (s, 2H), 3.65 (s, 2H), 3.33 (s, 3H), 2.80 (t, J=7.3 Hz, 2H), 2.49 (t, J=7.2 Hz, 2H), 2.27 (s, 3H), 2.08 (s, 3H), 1.45 (s, 9H). 19F NMR (CDCl3) δ-113.6 ppm. LC/MS (Method B): 546.4 (M+H)+. HPLC (Method A) Rt 5 min (Purity: 97.8%).

Workup

  1. customThe title compound was prepared following procedure
  2. filtrationThe reaction mixture was filtered through a SPE NH2 column (2 g)
  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)

Sources & evidence

ORD record
ord-bf67bb757d714480ba0a54997b74506e
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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