Morpholine → N-[3,5-Bis(trifluoromethyl)benzyl]-2-methyl-N-[2-(1-morpholin-4-ylethyl)-5-(trifluoromethyl)benzyl]-2H-tetrazol-5-amine

HRID 390742노트

반응식

HRID 390742 반응식
N1C2C=CC=C[C:4]=2N=N1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.[F:16][C:17]([F:50])([F:49])[C:18]1[CH:19]=[C:20]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:21][N:22]([CH2:29][C:30]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][C:31]=1[CH:32]=O)[C:23]1[N:24]=[N:25][N:26]([CH3:28])[N:27]=1>C(O)C>[F:48][C:45]([F:47])([F:46])[C:43]1[CH:42]=[C:20]([CH:19]=[C:18]([C:17]([F:49])([F:50])[F:16])[CH:44]=1)[CH2:21][N:22]([CH2:29][C:30]1[CH:37]=[C:36]([C:38]([F:41])([F:39])[F:40])[CH:35]=[CH:34][C:31]=1[CH:32]([N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[CH3:4])[C:23]1[N:24]=[N:25][N:26]([CH3:28])[N:27]=1

참가 물질

5

반응물 3

HCID 8083MorpholineHCID 589665242-{[(3,5-bis-trifluoromethyl-benzyl)(2-methyl-2H-tetrazol-5-yl)amino]-methyl}-4-trifluoromethyl-benzaldehydeHCID 178418385HCID 178418385, 화합물

생성물 1

HCID 58966509N-[3,5-Bis(trifluoromethyl)benzyl]-2-methyl-N-[2-(1-morpholin-4-ylethyl)-5-(trifluoromethyl)benzyl]-2H-tetrazol-5-amine수율 28%

시약·촉매·용매 1

HCID 702Ethanol용매2회

실험 절차

To a solution of benzotriazole (12.8 mg, 0.1075 mmoles) in ethanol (2 mL) was added morpholine (9.4 mg, 0.1075 mmoles) and the reaction was stirred for 10 minutes. A solution of 2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzaldehyde (50 mg, 0.0977 mmoles) in ethanol (1 mL) was added to the reaction mixture and it was further stirred for 16 hours. The imine fragment was observed MH+=581.4. Parent ion for the intermediate was not found. The ethanol was evaporated and the crude product was taken to the next step. Half of the crude was dissolved in toluene and methyl magnesium bromide (97 □L, 0.2916 mmoles of a 3M solution in ether) was added. The reaction mixture was heated at reflux for 2 hours. LC-MS indicated formation of product. The solvent was evaporated from the reaction mixture. 1N NaOH solution was added and the aqueous layer was extracted with dichloromethane. The organic layer was concentrated and the residue was dissolved in DMSO and purified on prepHPLC (Shimadzu, 30×50 C18, Basic, 30-95%, 0.1% NaOH, 8 min gradient, 220 UV) to yield 8.2 mg (28%) of the title compound as clear oil. MS (ES+) Calc: 596.4, Found: 597.2 (M+1).

후처리

  1. stirringwas further stirred for 16 hours
  2. customThe ethanol was evaporated
  3. dissolutionHalf of the crude was dissolved in toluene
  4. additionmethyl magnesium bromide (97 □L, 0.2916 mmoles of a 3M solution in ether) was added
  5. temperatureThe reaction mixture was heated
  6. temperatureat reflux for 2 hours
  7. customThe solvent was evaporated from the reaction mixture
  8. addition1N NaOH solution was added
  9. extractionthe aqueous layer was extracted with dichloromethane
  10. concentrationThe organic layer was concentrated
  11. dissolutionthe residue was dissolved in DMSO
  12. custompurified on prepHPLC (Shimadzu, 30×50 C18, Basic, 30-95%, 0.1% NaOH, 8 min gradient, 220 UV)

출처 및 근거

ORD 기록
ord-4be07b88af3a4ed19241713e1ea64f70
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383660B2

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