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Morpholine → 4-(5-(2-Fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-6-yl)morpholine

HRID 2195495
ノート
印刷プレビュー

反応式

HRID 2195495 の反応式
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][C:3]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=1[F:27].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.[OH-].[K+].[NH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1>C(O)(C)(C)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O>[F:27][C:19]1[CH:20]=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=[CH:23][C:18]=1[O:17][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[N:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1)[N:8]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:7]=[CH:6]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

9

反応物 4

HCID 8083MorpholineHCID 14797Potassium HydroxideHCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 667669036-Bromo-5-(2-fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

生成物 1

HCID 667671464-(5-(2-Fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-6-yl)morpholine収率 56.5%

試薬・触媒・溶媒

4
HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 6386tert-Butanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

To a solution of 6-bromo-5-(2-fluoro-4-nitro-phenoxy)-1-(tetrahydropyran-2-yl)-1 H-indazole (8.0 g, 18 mmol) in tert-butanol (150 mL) and H2O (3.2 mL) is added Pd2(dba)3 (320 mg, 0.35 mmol), 2-di-tert-butylphosphino-2′-methylbiphenyl (480 mg, 1.54 mmol), KOH (3.2 g, 57 mmol) and morpholine (3.2 g, 36.7 mmol) under N2. After the mixture is stirred at 70° C. for 2 hours under a N2 atmosphere, it is filtered and the filtrate is concentrated. The residue is partitioned with EtOAc (100 mL) and saturated aqueous NH4Cl (30 mL). The organic layer is separated, dried over MgSO4, and concentrated. The residue is purified by silica gel column chromatography eluting with PE:EtOAc (3:1) to give the product (4.5 g, 56.5% yield). MS (m/z): 443.1 (M+H).

後処理

  1. filtrationit is filtered
  2. concentrationthe filtrate is concentrated
  3. customThe residue is partitioned with EtOAc (100 mL) and saturated aqueous NH4Cl (30 mL)
  4. customThe organic layer is separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel column chromatography
  8. washeluting with PE

出典と根拠

ORDレコード
ord-08353c5945734795af231fcbbb324da2
出典データセット
uspto-grants-2012_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
USRE043878E1

反応ノート

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