Triethylamine → 3-[(1-Methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamide

HRID 548691노트

반응식

HRID 548691 반응식
[CH3:1][CH:2]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:13]=1)[C:8]([OH:10])=O)[CH3:3].C(Cl)(=O)C(Cl)=O.[CH3:28][N:29]1[CH:33]=[CH:32][C:31]([NH2:34])=[N:30]1.C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl>[CH3:3][CH:2]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:13]=1)[C:8]([NH:34][C:31]1[CH:32]=[CH:33][N:29]([CH3:28])[N:30]=1)=[O:10])[CH3:1]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1372541-Methyl-3-aminopyrazoleHCID 534011033-Benzyloxy-5-isopropoxybenzoic acid

생성물 1

HCID 536296253-[(1-Methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamide수율 99.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

실험 절차

DMF (2 drops) was added to a solution of 3-[(1-methylethyl)oxy]-5-[(phenylmethyl)oxy]benzoic acid (40.0 g, 0.14 mol) and oxalyl chloride (14.6 mL, 0.17 mol) in DCM (700 mL). The mixture was stirred at ambient temperature for 4 hours and the DCM and excess oxalyl chloride were evaporated in vacuo. The residual acid chloride was dissolved in DCM (300 mL) and added dropwise to 1-methyl-3-aminopyrazole (14.25 g, 0.147 mol) and triethylamine (41 mL, 0.29 mol) in DCM (300 mL), at 0° C. Stirred at ambient temperature for 24 hours. The DCM was evaporated in vacuo, and the residue partitioned between ethyl acetate (400 mL) and 1N hydrochloric acid (200 mL). The ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (200 mL) and brine (100 mL), dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 50% ethyl acetate in isohexane, to give the desired compound (51 g). 1H NMR δ (CDCl3): 1.30 (d, 6H), 3.61 (s, 3H), 4.50 (sept, 1H), 5.01 (s, 2H), 6.66 (m, 1H), 6.88 (m, 1H), 7.00 (m, 1H), 7.06 (m, 1H), 7.24 (m, 1H), 7.39 (m, 5H), 9.50 (s, 1H). m/z 366 (M+H)+

후처리

  1. customthe DCM and excess oxalyl chloride were evaporated in vacuo
  2. dissolutionThe residual acid chloride was dissolved in DCM (300 mL)
  3. stirringStirred at ambient temperature for 24 hours
  4. customThe DCM was evaporated in vacuo
  5. customthe residue partitioned between ethyl acetate (400 mL) and 1N hydrochloric acid (200 mL)
  6. washThe ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (200 mL) and brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on silica
  10. washeluting with a gradient of 50% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-7a3c2ef9ff4647f0a8bcea4b074817c5
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943607B2

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