Diisopropylethylamine → 1-(2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetoyl)piperidine-3-carbonitrile

HRID 1775559

반응식

HRID 1775559 반응식
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:23][C:24]([OH:26])=O)[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:3]=12.[NH:27]1[CH2:32][CH2:31][CH2:30][CH:29]([C:33]#[N:34])[CH2:28]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:23][C:24]([N:27]3[CH2:32][CH2:31][CH2:30][CH:29]([C:33]#[N:34])[CH2:28]3)=[O:26])[N:15]=[C:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:3]=12

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 420926Piperidine-3-carbonitrileHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 665757822-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetic acid

생성물 1

HCID 665759381-(2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetoyl)piperidine-3-carbonitrile수율 22.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of 2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetic acid (100 mg, 0.27 mmol) in DMF (2 mL) were added piperidine-3-carbonitrile (33 mg, 0.30 mmol), diisopropylethylamine (DIPEA) (105 μL, 0.60 mmol) and 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (125 mg, 0.33 mmol). The solution obtained was stirred at room temperature for 18 h then diluted with EtOAc. The organic phase was washed with water and brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by preparative HPLC followed by a second chromatography purification (silica gel, gradient 1/1 ethyl acetate/isohexane) yielding Compound 58 as a solid (28 mg).

후처리

  1. customThe solution obtained
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by preparative HPLC
  6. customfollowed by a second chromatography purification (silica gel, gradient 1/1 ethyl acetate/isohexane)

출처 및 근거

ORD 기록
ord-a572e8d599d0462c80621086d4ddbc37
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09260381B2

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