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1,2-Dichloroethane → tert-butyl (3S)-3-[{(7R)-14-cyclohexyl-11-[({[(2,2-dimethoxyethyl)(methyl)amino]sulfonyl}amino)carbonyl]-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl}(methyl)amino]pyrrolidine-1-carboxylate

HRID 1669466
ノート
印刷プレビュー

反応式

HRID 1669466 の反応式
[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C@H:12]([N:15]([CH3:45])[C@@H:16]2[CH2:23][N:22]3[C:24]4[CH:25]=[C:26]([C:37](OC)=[O:38])[CH:27]=[CH:28][C:29]=4[C:30]([CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[C:21]3[C:20]3[CH:41]=[CH:42][CH:43]=[CH:44][C:19]=3[O:18][CH2:17]2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl.C(Cl)CCl.[CH3:51][O:52][CH:53]([O:61][CH3:62])[CH2:54][N:55]([CH3:60])[S:56]([NH2:59])(=[O:58])=[O:57]>O1CCOCC1.C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:31]1([C:30]2[C:29]3[CH:28]=[CH:27][C:26]([C:37]([NH:59][S:56]([N:55]([CH2:54][CH:53]([O:52][CH3:51])[O:61][CH3:62])[CH3:60])(=[O:58])=[O:57])=[O:38])=[CH:25][C:24]=3[N:22]3[C:21]=2[C:20]2[CH:41]=[CH:42][CH:43]=[CH:44][C:19]=2[O:18][CH2:17][C@H:16]([N:15]([CH3:45])[C@H:12]2[CH2:13][CH2:14][N:10]([C:8]([O:7][C:3]([CH3:4])([CH3:6])[CH3:5])=[O:9])[CH2:11]2)[CH2:23]3)[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 67346364methyl (7R)-7-[[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylateHCID 86627889N-(2,2-dimethoxyethyl)-N-methylsulfamide

生成物 1

HCID 67344852
tert-butyl (3S)-3-[{(7R)-14-cyclohexyl-11-[({[(2,2-dimethoxyethyl)(methyl)amino]sulfonyl}amino)carbonyl]-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl}(methyl)amino]pyrrolidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
75 °C

実験手順

1M KOH (3.5 eq) was added to a 0.3M solution of methyl (7R)-7-[[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (1 eq) in dioxane and the mixture was stirred at 75° C. for 12 h. The pH was adjusted at 0° C. by addition of 1N HCl (until pH=6), then all volatiles were evaporated, the solid residue was taken in CHCl3 and salt was filtered off. The filtrate was concentrated in vacuo to afford a residue that was taken in dry DCM (0.05M); DMAP (3.5 eq), EDC (1.5 eq) and N-(2,2-dimethoxyethyl)-N-methylsulfamide (1.5 eq; prepared as described in Example 1, step 1) were added and the mixture was stirred at 40° C. for 1 h. The residue obtained after evaporation was extracted with EtOAc. The combined organic phases were washed with 1M HCl, sat. aq. NaHCO3 and brine, dried over Na2SO4 and concentrated to afford the title compound which was used without further purification. (ES+) m/z 754 (M+H)+.

後処理

  1. customall volatiles were evaporated
  2. filtrationsalt was filtered off
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto afford a residue that
  5. stirringthe mixture was stirred at 40° C. for 1 h
  6. customThe residue obtained
  7. customafter evaporation
  8. extractionwas extracted with EtOAc
  9. washThe combined organic phases were washed with 1M HCl, sat. aq. NaHCO3 and brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-6aa9a0985fb445bfb39565bac8ac94b1
出典データセット
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07989438B2

反応ノート

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