Triethylamine → tert-Butyl 2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

HRID 1913460노트

반응식

HRID 1913460 반응식
Cl.[CH2:2]1[C:5]2([CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]2)[CH2:4][NH:3]1.[N:18]1[CH:23]=[CH:22][CH:21]=[N:20][C:19]=1[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[C:29](=O)[CH2:28][CH2:27]2.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[N:18]1[CH:23]=[CH:22][CH:21]=[N:20][C:19]=1[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[CH:29]([N:3]1[CH2:4][C:5]3([CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10]3)[CH2:2]1)[CH2:28][CH2:27]2

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 45489808Tert-butyl 2,7-diazaspiro(3.5)nonane-7-carboxylate hydrochlorideHCID 584384795-Pyrimidin-2-yl-indan-1-one

생성물 1

HCID 77287501tert-Butyl 2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate수율 57.8%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 6344Dichloromethane용매

실험 절차

To a solution of tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate hydrochloride (850 mg, 3.23 mmol) and 5-pyrimidin-2-ylindan-1-one (SM-1b, 680 mg, 3.23 mmol) in dichloromethane (10 mL) under nitrogen was added triethylamine (2.5 mL, 17.9 mmol) followed by titanium isopropoxide (2.9 mL, 9.70 mmol). The reaction was stirred at room temperature for 90 minutes and sodium triacetoxyborohydride (2.1 g, 9.9 mmol) was added. After stirring for 4 days, the reaction was quenched with saturated ammonium chloride. The mixture was diluted with 50 mL of dichloromethane and 50 mL of water and filtered through a Celite® pad. The aqueous layer was extracted with dichloromethane (2×30 mL). The combined organics layers were washed with brine and dried over MgSO4. The solvent was removed to give a dark green/brown paste which was chromatographed on a Combiflash ISCO purification system (Teledyne Corp., Lincoln Nebr.) using a dichloromethane/MeOH gradient to afford the title compound as light brown oil (785 mg, 57.7%). MS (ES+) 421.2 (M+H)+. 1H NMR (CDCl3) δ 1.39 (s, 9H), 1.59-1.69 (m, 4H), 1.75-1.94 (m, 1H), 2.12 (dq, 1H), 2.76-2.92 (m, 1H), 2.95-3.18 (m, 5H), 3.19-3.36 (m, 4H), 3.92 (dd, 1H), 7.09 (t, 1H), 7.33 (d, 1H), 8.18-8.26 (m, 2H), 8.71 (d, 2H).

후처리

  1. stirringAfter stirring for 4 days
  2. customthe reaction was quenched with saturated ammonium chloride
  3. additionThe mixture was diluted with 50 mL of dichloromethane and 50 mL of water
  4. filtrationfiltered through a Celite® pad
  5. extractionThe aqueous layer was extracted with dichloromethane (2×30 mL)
  6. washThe combined organics layers were washed with brine
  7. dry with materialdried over MgSO4
  8. customThe solvent was removed
  9. customto give a dark green/brown paste which
  10. customwas chromatographed on a Combiflash ISCO purification system (Teledyne Corp., Lincoln Nebr.)

출처 및 근거

ORD 기록
ord-f7942d0a169f442697119aa10c10fb04
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609680B2

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