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

HRID 2195495
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HRID 2195495 반응식
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
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참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매

4
HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 6386tert-Butanol용매HCID 8857Ethyl Acetate용매

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온도
70 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-08353c5945734795af231fcbbb324da2
출처 데이터셋
uspto-grants-2012_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
USRE043878E1

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