Tris(1,1-dimethylethyl)phosphine → N-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]-N-methyl-1-[2-(trimethylsilyl)-ethoxy]methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine

HRID 2056350노트

반응식

HRID 2056350 반응식
[CH2:1]([N:8]1[CH2:13][CH2:12][C@@H:11]([CH3:14])[C@@H:10]([NH:15][CH3:16])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:18]1[CH:23]=[CH:22][N:21]=[C:20]2[N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:25]=[CH:26][C:19]=12.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C(OCC)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C@@H:11]([CH3:14])[C@@H:10]([N:15]([CH3:16])[C:18]2[CH:23]=[CH:22][N:21]=[C:20]3[N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:25]=[CH:26][C:19]=23)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

9

반응물 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 116735894-Chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo(2,3-b)pyridineHCID 23676156Sodium t-butoxideHCID 44630604(3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine

생성물 1

HCID 66662878N-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]-N-methyl-1-[2-(trimethylsilyl)-ethoxy]methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine수율 120.8%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
70 °C

실험 절차

A degassed mixture of (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine (0.210 g, 0.000962 mol), 4-chloro-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine (0.29 g, 0.0010 mol), tris(dibenzylideneacetone)dipalladium(0) (0.088 g, 0.000096 mol), 0.049 M of tri-tert-butylphosphine in toluene (1.0 mL) and sodium tert-butoxide (0.139 g, 0.00144 mol) in toluene (3 mL, 0.03 mol) was heated to 70° C. for 5 h. After the reaction mixture was cooled to room temperature (rt), ethyl acetate and water were added. The resulting suspension was filtered. The aqueous phase was removed and the remaining organic phase was washed with sat. NaCl, dried, and concentrated under vacuum to give 540 mg orange oil. The crude product was chromatographed using 35% ethyl acetate/hex to give 280 mg orange oil (˜1:1 of two isomers). The mixture was chromatographed again with 35% ethyl acetate/hex several times to separate 44 mg of the higher Rf material.

후처리

  1. additionwere added
  2. filtrationThe resulting suspension was filtered
  3. customThe aqueous phase was removed
  4. washthe remaining organic phase was washed with sat. NaCl
  5. customdried
  6. concentrationconcentrated under vacuum

출처 및 근거

ORD 기록
ord-9f22598e2bd047129df955d73eb47dcf
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07335667B2

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