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4-Aminotetrahydropyran → 4-(6,6-Dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzonitrile

HRID 602401
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인쇄 미리보기

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HRID 602401 반응식
[NH2:1][CH:2]1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.CC(C)([O-])C.[Na+].Br[C:15]1[CH:22]=[C:21]([N:23]2[C:31]3[CH2:30][C:29]([CH3:33])([CH3:32])[CH2:28][C:27](=[O:34])[C:26]=3[C:25]([C:35]([F:38])([F:37])[F:36])=[N:24]2)[CH:20]=[CH:19][C:16]=1[C:17]#[N:18]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH3:32][C:29]1([CH3:33])[CH2:30][C:31]2[N:23]([C:21]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[C:15]([NH:1][CH:2]4[CH2:7][CH2:6][O:5][CH2:4][CH2:3]4)[CH:22]=3)[N:24]=[C:25]([C:35]([F:37])([F:38])[F:36])[C:26]=2[C:27](=[O:34])[CH2:28]1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 3

HCID 4192234-AminotetrahydropyranHCID 118541752-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrileHCID 23676156Sodium t-butoxide

생성물 1

HCID 669529694-(6,6-Dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzonitrile수율 147.5%

시약·촉매·용매 5

HCID 167845
palladium(II) acetate
촉매
HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매
HCID 962Water용매
HCID 1140Toluene용매
HCID 8857Ethyl Acetate용매

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온도
120 °C

실험 절차

4-Aminotetrahydropyran (245 mg, 2.42 mmol, 2.0 eq) and sodium tert-butoxide (233 mg, 2.42 mmol, 2.0 eq) were added to a stirred solution/suspension of 2-bromo-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (500 mg, 1.21 mmol, 1.0 eq), palladium (II) acetate (14 mg, 0.06 mmol, 0.05 eq), and DPPF (67 mg, 0.12 mmol, 0.10 eq) in 3.75 mL of toluene. The reaction vial was capped, and the reaction mixture was heated 20 minutes at 120° C. under microwave irradiation. The reaction mixture was diluted with water and ethyl acetate and combined. The layers were separated, and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified on a Biotage system (SiO2, hexanes-ethyl acetate) to afford 4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzonitrile (772 mg, 49%) as a tan solid: LC/MS (m/z): [M+H]+ 433.7. Further elution with ethyl acetate afforded 4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide (713 mg, 44%) as a yellow solid: LC/MS (m/z): [M+H]+ 451.2.

후처리

  1. customThe reaction vial was capped
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on a Biotage system (SiO2, hexanes-ethyl acetate)

출처 및 근거

ORD 기록
ord-9baed685dccd44f5b34f597c89eeb579
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906529B2

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