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Ammonia → tert-Butyl (3R)-4-[3-(2-{[2-(2-{2-[(tert-butoxycarbonyl)amino]ethoxy}-ethoxy)pyridin-3-yl]oxy}ethoxy)pyrazin-2-yl]-3-methylpiperazine-1-carboxylate

HRID 1765092
ノート
印刷プレビュー

反応式

HRID 1765092 の反応式
O1CCCCC1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:12]([O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[N:13][CH:14]=[CH:15][CH:16]=1.N.CC(C)([O-])C.[K+].Cl[C:39]1[C:40]([N:45]2[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][C@H:46]2[CH3:58])=[N:41][CH:42]=[CH:43][N:44]=1>CC(O)=O.[Cl-].[Na+].O.O.[Cl-].[Na+].O.C(#N)C>[C:26]([O:25][C:24]([NH:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18][O:17][C:12]1[C:11]([O:10][CH2:9][CH2:8][O:7][C:39]2[C:40]([N:45]3[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][C@H:46]3[CH3:58])=[N:41][CH:42]=[CH:43][N:44]=2)=[CH:16][CH:15]=[CH:14][N:13]=1)=[O:30])([CH3:29])([CH3:28])[CH3:27]
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 4

HCID 222AmmoniaHCID 23665647Potassium tert-butoxideHCID 86591089tert-Butyl {2-[2-({3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}carbamateHCID 86591091(R)-tert-butyl 4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate

生成物 1

HCID 86591090tert-Butyl (3R)-4-[3-(2-{[2-(2-{2-[(tert-butoxycarbonyl)amino]ethoxy}-ethoxy)pyridin-3-yl]oxy}ethoxy)pyrazin-2-yl]-3-methylpiperazine-1-carboxylate
収率 40.9%

試薬・触媒・溶媒 4

HCID 176Acetic Acid溶媒HCID 6342Acetonitrile溶媒HCID 23713072Sodium chloride dihydrate溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
50 °C

実験手順

tert-Butyl {2-[2-({3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}carbamate (from Step 1; 0.74 g, 1.7 mmol) was suspended in 2 M HOAc (5 mL) and acetonitrile (1 mL) and heated at 50° C. for two days. The solution was neutralized with concentrated aqueous ammonia. Brine was added (3 mL) and the mixture was extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4) and the solvent was removed under reduced pressure. The remaining oil was dissolved in dry DMSO (10 mL), potassium tert-butoxide (0.36 g, 3.2 mmol) was added followed by tert-butyl (3R)-4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate (from Example 5; 0.59 g, 1.9 mmol) and the mixture was heated at 50° C. for 20 minutes. The reaction mixture was diluted with water/brine (90:10) and extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4), the solvent was removed under reduced pressure and the remaining oil was chromatographed on a column of silica with hexane/EtOAc (70:30) as eluent to give 0.43 g (40%) of the title compound as a colorless oil. LC-UV purity: system (A) 100%. HRMS m/z calcd for C30H46N6O8 (M)+ 618.3377. found 618.3381. Step 3: {2-[2-({3-[2-({3-[(2R)-2-Methylpiperazin-1-yl]pyrazin-2-yl}oxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}amine, bis(trifluoroacetate).

後処理

  1. extractionthe mixture was extracted with CHCl3 (×3)
  2. dry with materialThe combined organic phases were dried (MgSO4)
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe remaining oil was dissolved in dry DMSO (10 mL)
  5. extractionextracted with CHCl3 (×3)
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. customthe solvent was removed under reduced pressure
  8. customthe remaining oil was chromatographed on a column of silica with hexane/EtOAc (70:30) as eluent

出典と根拠

ORDレコード
ord-ac43c76598564435954e6bf2c483f564
出典データセット
uspto-grants-2007_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07226925B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート