Triethylamine → N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(Methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-N'-[4-(1H-pyrazol-1-yl)phenyl]urea

HRID 1009949노트

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HRID 1009949 반응식
[N:1]1([C:6]2[CH:14]=[CH:13][C:9](C(O)=O)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.C([N:17]([CH2:20]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])C=CC=CC=1.Cl.Cl.[CH3:41][O:42][CH2:43][C@H:44]1[C@H:53]2[CH2:54][CH2:55][N:56]([C:57]([C@H:59]3[CH2:64][CH2:63][CH2:62][CH2:61][C@H:60]3[NH2:65])=[O:58])[C@H:52]2[C:51]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[NH:45]1>C1(C)C=CC=CC=1.O1CCCC1.O>[CH3:41][O:42][CH2:43][C@H:44]1[C@H:53]2[CH2:54][CH2:55][N:56]([C:57]([C@H:59]3[CH2:64][CH2:63][CH2:62][CH2:61][C@H:60]3[NH:65][C:20]([NH:17][C:9]3[CH:8]=[CH:7][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:14][CH:13]=3)=[O:29])=[O:58])[C@H:52]2[C:51]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[NH:45]1

참가 물질

8

반응물 4

HCID 8471Triethylamine2회HCID 199401P,P-Diphenylphosphinic azideHCID 7365274-(1H-pyrazol-1-yl)benzoic acidHCID 67150533(1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexaneamine dihydrochloride

생성물 1

HCID 57847222N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(Methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-N'-[4-(1H-pyrazol-1-yl)phenyl]urea수율 76.5%

시약·촉매·용매 3

HCID 962Water용매HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

To a suspension of 4-(1H-pyrazol-1-yl)benzoic acid (271 mg, 1.44 mmol) in toluene (5 ml) were added triethylamine (0.200 ml, 1.44 mmol) and diphenylphosphorylazide (0.310 ml, 1.44 mmol) at room temperature, and the mixture was stirred at 80° C. for 2 hrs. This reaction mixture was allowed to cool to room temperature and added dropwise to a solution of (1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexaneamine dihydrochloride (200 mg, 0.480 mmol) and triethylamine (0.200 ml, 1.44 mmol) in tetrahydrofuran (5 ml). The mixture was stirred at room temperature for 3 hrs., water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution, dried over anhydrous MgSO4, and concentrated under reduced pressure. The obtained residue was subjected to column chromatography using silica gel and eluted with hexane-ethyl acetate (5:5-0:1) to give the title compound (194 mg, 76%) as an amorphous form.

후처리

  1. temperatureto cool to room temperature
  2. stirringThe mixture was stirred at room temperature for 3 hrs
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated under reduced pressure
  7. washeluted with hexane-ethyl acetate (5:5-0:1)

출처 및 근거

ORD 기록
ord-e03bbed28e2744fea8b807b3163f9abb
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07973163B2

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