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 550308

反応式

HRID 550308 の反応式
[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

参加物

8

反応物 4

HCID 8471Triethylamine2 回HCID 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

生成物 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]urea収率 76.5%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ab2d7521990c4acb96b24af3cee7d752
出典データセット
uspto-grants-2011_05
特許番号
US07943770B2

関連ノート

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