Triethylamine → tert-Butyl 4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidine-1-carboxylate

HRID 16594

반응식

HRID 16594 반응식
[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]1=[O:13])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[C:22](Cl)([O:24]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:33][CH2:34][CH:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]1.C([O-])(O)=O.[Na+]>O1CCCC1>[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:22]([NH:33][CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)=[O:24])[C:5]1=[O:13])([CH3:3])[CH3:2]

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 16535801-(Propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-one

생성물 1

HCID 59428174tert-Butyl 4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidine-1-carboxylate수율 62%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

To a stirred solution of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2one (J. Med. Chem. 1999, 42, 2870-2880) (3.00 g, 17.02 mmol) and triethylamine (7.12 ml, 51.06 mmol) in 70 ml tetrahydrofuran was added triphosgene (5.15 g, 17.02 mmol) in 14 ml tetrahydrofuran at room temperature. The reaction mixture was refluxed for 19 hours. The mixture was then cooled to room temperature, tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (J. Prugh, L. A. Birchenough and M. S. Egbertson, Synth. Commun., 1992, 22, 2357-60) (3.28 g, 15.32 mmol) in 10 ml tetrahydrofuran was added. The reaction mixture was refluxed for another 24 hours. Then cooled and basified with aqueous saturated NaHCO3 50 ml, and extracted with ethyl acetate 100 ml for three times. The combined extract was washed with brine, dried over MgSO4 and concentrated. Flash chromatography of the residue (elutent: hexane/ethyl acetate=5/1 to 1/2) afforded a colorless oil 3.99 g (62%) as the titled compound.

후처리

  1. temperatureThe reaction mixture was refluxed for 19 hours
  2. temperatureThe reaction mixture was refluxed for another 24 hours
  3. temperatureThen cooled
  4. extractionextracted with ethyl acetate 100 ml for three times
  5. extractionThe combined extract
  6. washwas washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-d910c26976774feaaab89c491a09e3af
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737163B2

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