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Ammonium Chloride → 8-(2,4-Difluorophenoxy)-7-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one

HRID 1056978
ノート
印刷プレビュー

反応式

HRID 1056978 の反応式
[F:1][C:2]1[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:3]=1[O:4][C:5]1[C:6]([N+:36]([O-])=O)=[C:7]([NH:30][CH2:31][C:32](OC)=[O:33])[CH:8]=[CH:9][C:10]=1[C:11]1[C:12]2[CH:21]=[N:20][N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:13]=2[C:14](=[O:18])[N:15]([CH3:17])[CH:16]=1.[Cl-].[NH4+]>C(OCC)(=O)C.CO.ClCCl.[Zn]>[F:1][C:2]1[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:3]=1[O:4][C:5]1[C:10]([C:11]2[C:12]3[CH:21]=[N:20][N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:13]=3[C:14](=[O:18])[N:15]([CH3:17])[CH:16]=2)=[CH:9][CH:8]=[C:7]2[C:6]=1[NH:36][C:32](=[O:33])[CH2:31][NH:30]2
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

7

反応物 2

HCID 25517Ammonium ChlorideHCID 131736451Methyl {[3-(2,4-difluorophenoxy)-4-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)-2-nitrophenyl]amino}acetate

生成物 1

HCID 1232172868-(2,4-Difluorophenoxy)-7-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one収率 24.3%

試薬・触媒・溶媒 4

HCID 23994
Zinc
触媒
HCID 887Methanol溶媒
HCID 6344Dichloromethane溶媒2 回
HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A suspension of methyl {[3-(2,4-difluorophenoxy)-4-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)-2-nitrophenyl]amino}acetate (0.048 g, 0.078 mmol) in ethyl acetate (0.452 mL) and methanol (0.452 mL) was cooled to 0° C. and then treated with saturated ammonium chloride solution (0.0679 mL, 1.01 mmol) at that temperature. Zinc (0.0408 g, 0.624 mmol) was added to the reaction mixture in two portions over 5 min and the reaction mixture was stirred at RT for 16 h. The reaction mixture was diluted with dichloromethane and filtered through a pad of Celite. The solids were washed with additional dichloromethane and the filtrate was concentrated in vacuo to yield a crude residue. The residue was dissolved in dichloromethane and the organic phase was washed with saturated sodium bicarbonate solution, dried with sodium sulfate, filtered, and concentrated in vacuo to give the crude product. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (10.5 mg, 24%) along with a small amount of the oxidized product, 8-(2,4-difluorophenoxy)-7-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)quinoxalin-2(1H)-one. This mixture was used in the next step without separation. LCMS calculated for C27H30F2N5O4Si (M+H)+: m/z=554.2. found: 554.1.

後処理

  1. filtrationfiltered through a pad of Celite
  2. washThe solids were washed with additional dichloromethane
  3. concentrationthe filtrate was concentrated in vacuo
  4. customto yield a crude residue
  5. washthe organic phase was washed with saturated sodium bicarbonate solution
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product
  10. customPurification via preparative LCMS (XBridge C18 column
  11. washeluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

出典と根拠

ORDレコード
ord-a6bbd9fb381747e2b0e6cbbbce35fcbe
出典データセット
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09399640B2

反応ノート

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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