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Acetic Acid → 1,4-Dibutyl-3-{6-[2-(1H-tetrazol-5-yl)-phenyl]-pyridin-3-ylmethyl}-1,3-dihydro-imidazol-2-one

HRID 263432
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HRID 263432 반응식
C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3B(O)O)=[N:11][N:10]=[N:9]2)C=CC=CC=1.[CH2:34]([N:38]1[CH:42]=[C:41]([CH2:43][CH2:44][CH2:45][CH3:46])[N:40]([CH2:47][C:48]2[CH:49]=[N:50][C:51](Br)=[CH:52][CH:53]=2)[C:39]1=[O:55])[CH2:35][CH2:36][CH3:37].C(=O)([O-])[O-].[Na+].[Na+].C(O)(=O)C>C(O)C.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:34]([N:38]1[CH:42]=[C:41]([CH2:43][CH2:44][CH2:45][CH3:46])[N:40]([CH2:47][C:48]2[CH:49]=[N:50][C:51]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[NH:8][N:9]=[N:10][N:11]=3)=[CH:52][CH:53]=2)[C:39]1=[O:55])[CH2:35][CH2:36][CH3:37]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 103427452-(1-Trityl-1H-tetrazol-5-YL)phenylboronic acidHCID 154057291,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl)methyl]-2H-imidazol-2-one

생성물 1

HCID 1784412521,4-Dibutyl-3-{6-[2-(1H-tetrazol-5-yl)-phenyl]-pyridin-3-ylmethyl}-1,3-dihydro-imidazol-2-one수율 43%

시약·촉매·용매

3
HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매2회HCID 1140Toluene용매2회

실험 절차

A solution of 21.7 g (50.2 mmol) of 2-(N-triphenylmethyltetrazol-5-yl)phenylboronic acid from step 6 in 80 mL of ethanol and 130 mL of toluene was added to a mixture of 5 g (4 mmol) of tetrakis (triphenylphosphine) Pd(0), 16.75 g (45.8 mmol) of 1,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl)methyl]-2H-imidazol-2-one from step 5, 225 mL of toluene, 100 mL of 2M sodium carbonate, and 150 mL of ethanol. The reaction mixture was heated to reflux and vigorously stirred under nitrogen for 14 h. The pH was adjusted to 6 with acetic acid and the reaction concentrated in vacuo. The product was.purified by silica gel chromatography (Waters Prep-500A) using 2-propanol/methylene chloride (0-50%) followed by reverse phase chromatography (Waters Deltaprep-3000) using acetonitrile/water (30-35:70-65) (0.05% TFA). The pure fractions (by analytical HPLC) were combined, the acetonitrile removed in vacuo, and the water extracted 4 times with chloroform. The extracts were combined, dried (MgSO4), and concentrated in vacuo. Recrystallization from ethyl acetate gave 8.5 g (43%) of colorless 1,4-dibutyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one as a colorless solid: mp 170°-171° C.; NMR (CDCl3) δ 0.88 (t, J=7 Hz, 3H), 0.96 (t, J=7 Hz, 3H), 1.28-1.54 (m, 6H), 1.61-1.72 (m, 2H), 2.28 (t, J=8 Hz, 2H), 3.63 (t, J=7 Hz, 2H), 4.96 (s, 2H), 5.96 (s, 1H), 7.36 (d, J=9 Hz, 1H), 7.47-7.58 (m, 3H), 7.67 (dd, J=9 and 2 Hz, 1H), 8.06-8.13 (m, 1H), 8.52 (d, J=2 Hz, 1H); MS (FAB) m/e (rel intensity) 432 (100), 404 (18), 237 (14), 209 (92), 180 (82); HRMS. Calc'd for M+H: 432.2512. Found: 432.2554. Anal. Calc'd for C24H29N7O: C, 66.80; H, 6.77; N, 22.72. Found: C, 66.59; H, 6.85; N, 22.57.

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. concentrationthe reaction concentrated in vacuo
  4. customthe acetonitrile removed in vacuo
  5. extractionthe water extracted 4 times with chloroform
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customRecrystallization from ethyl acetate

출처 및 근거

ORD 기록
ord-896a9ec64b894464990015569e3d76db
출처 데이터셋
uspto-grants-1997_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05643906

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