Acetic Acid → [4-Cyclopropanesulfonylaminocarbonyl-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-14-yl]-carbamic acid tert-butyl ester

HRID 346940ノート

反応式

HRID 346940 の反応式
[C:1]([O:5][C:6](=[O:49])[NH:7][CH:8]1[C:26](=[O:27])[N:25]2[CH:21]([CH2:22][CH:23]([O:28][C:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:32]=[CH:31][N:30]=3)[CH2:24]2)[C:20](=[O:39])[NH:19][C:18]2([C:40]([NH:42][S:43]([CH:46]3[CH2:48][CH2:47]3)(=[O:45])=[O:44])=[O:41])[CH:16]([CH2:17]2)[CH:15]=[CH:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].N(C([O-])=O)=NC([O-])=O.[K+].[K+].C(O)(=O)C>CO>[C:1]([O:5][C:6](=[O:49])[NH:7][CH:8]1[C:26](=[O:27])[N:25]2[CH:21]([CH2:22][CH:23]([O:28][C:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:32]=[CH:31][N:30]=3)[CH2:24]2)[C:20](=[O:39])[NH:19][C:18]2([C:40]([NH:42][S:43]([CH:46]3[CH2:48][CH2:47]3)(=[O:44])=[O:45])=[O:41])[CH:16]([CH2:17]2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 176Acetic Acid2 回HCID 6096233Potassium diazene-1,2-dicarboxylate2 回HCID 72804543[4-Cyclopropane-sulfonylaminocarbonyl-18-(isoquinolin 1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester

生成物 1

HCID 72427494[4-Cyclopropanesulfonylaminocarbonyl-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-14-yl]-carbamic acid tert-butyl ester収率 57.3%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

実験手順

To a mixture of 140 mg (0.2 mmol) of [4-cyclopropanesulfonylaminocarbonyl-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester in 3 mL of methanol was added 656 mg (4 mmol)of dipotassium azodicarboxylate. Glacial acetic acid (480 mg, 8 mmol)in 2 mL of methanol was added slowly by a syringe pump over 5 h. The mixture was stirred at rt. After 5 h, another 656 mg (4 mmol) of dipotassium azodicarboxylate and 480 mg (8 mmol) of glacial acetic acid was added over the course of 5 h and the stirring was continued overnight. This cycle was repeated twice. LC-MS showed about 40% starting material still was remaining. The solvent was then removed on a rotary evaporator. Water was added to the residue and the mixture was extracted three times with ethyl acetate. It was then dried with magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was dissolved in methanol and purified by preparative HPLC (YMC XTERRA, S5, 30×50 mm, gradient: 72% B to 78% B, 15 min, hold 2 min, flow rate 40 ml/min) to isolate the product as a white powder (80 mg, 57%). LC-MS (Method A, retention time: 3.59 min), MS m/z 698 (M++1).

後処理

  1. waitthe stirring was continued overnight
  2. customThe solvent was then removed on a rotary evaporator
  3. additionWater was added to the residue
  4. extractionthe mixture was extracted three times with ethyl acetate
  5. dry with materialIt was then dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resulting oil was dissolved in methanol
  9. custompurified by preparative HPLC (YMC XTERRA, S5, 30×50 mm, gradient: 72% B to 78% B, 15 min, hold 2 min, flow rate 40 ml/min)

出典と根拠

ORDレコード
ord-a0fbe69910e645779f1a3703218d2393
出典データセット
uspto-grants-2007_02
特許番号
US07173004B2

反応ノート

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