Nitrogen → Methyl 4-[3-(2,2'-dimethylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

HRID 219908ノート

反応式

HRID 219908 の反応式
[CH3:1][C:2]1[CH:7]=[C:6](C(O)=O)[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17].[NH2:18][C:19](=[N:31][OH:32])[C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([F:30])[CH:21]=1.Cl.[CH2:34](N=C=NCCCN(C)C)C.N#N.C(N(C(C)C)C(C)C)C>C1COCC1.CC#N>[CH3:17][C:12]1[CH:13]=[C:14]([C:19]2([C:20]3[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([F:30])[CH:21]=3)[N:18]=[CH:34][O:32][NH:31]2)[CH:15]=[CH:16][C:11]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1]

参加物

8

反応物 5

HCID 947NitrogenHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219373032,2'-Dimethyl-[1,1'-biphenyl]-4-carboxylic acidHCID 76644654Methyl 4-[amino(hydroxyimino)methyl]-2-fluorobenzoate

生成物 1

HCID 67542198Methyl 4-[3-(2,2'-dimethylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Intermediate 3 (814 mg; 3.60 mmol; 1.20 eq.), Intermediate 1 (637 mg; 3 mmol; 1 eq.) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (690 mg; 3.60 mmol; 1.20 eq.) were dissolved in THF (10 mL) and CH3CN (10 mL) in a 20 mL microwave vial under N2. The reaction mixture was stirred overnight at RT. Then n-ethyldiisopropylamine (DIEA) (1.22 mL; 7.20 mmol; 2.40 eq.) was added and the mixture was heated in the microwave at 150° C. for 30 min. The reaction mixture was evaporated to dryness. EtOAc (50 mL) was added and the mixture was washed with HCl 0.1 N (2×25 mL), a saturated aqueous solution of NaHCO3 (25 mL) and dried over MgSO4. After evaporation of the solvents, the resulting crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5), affording the title compound as a white powder. 1H NMR (DMSO-d6, 300 MHz) δ 8.17-8.16 (m, 1H), 8.12 (d, J=7.2 Hz, 1H), 8.29-8.04 (m, 2H), 7.98 (dd, J=11.1, 2.5 Hz, 1H), 7.39-7.27 (m, 4H), 7.14-7.11 (m, 1H), 3.91 (s, 3H), 2.13 (s, 3H), 2.03 (s, 3H). LC/MS (Method A): 403.0 (M+H)+. HPLC (Method A) Rt 6.23 min (Purity: 93.5%).

後処理

  1. temperaturethe mixture was heated in the microwave at 150° C. for 30 min
  2. customThe reaction mixture was evaporated to dryness
  3. additionEtOAc (50 mL) was added
  4. washthe mixture was washed with HCl 0.1 N (2×25 mL)
  5. dry with materiala saturated aqueous solution of NaHCO3 (25 mL) and dried over MgSO4
  6. customAfter evaporation of the solvents
  7. customthe resulting crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5)

出典と根拠

ORDレコード
ord-acf0198879924c0aa776729dfa40628e
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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