Diisopropylethylamine → 1-[5-(4-Amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanone

HRID 1910067Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1910067
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[C:20]4[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=4[N:14]([CH3:22])[CH:13]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[F:23][C:24]([F:36])([F:35])[C:25]1[N:30]=[C:29]([CH2:31][C:32](O)=[O:33])[CH:28]=[CH:27][CH:26]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O.O>[CH3:22][N:14]1[C:15]2[N:16]=[CH:17][N:18]=[C:19]([NH2:21])[C:20]=2[C:12]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[N:3]([C:32](=[O:33])[CH2:31][C:29]2[CH:28]=[CH:27][CH:26]=[C:25]([C:24]([F:23])([F:36])[F:35])[N:30]=2)[CH2:4][CH2:5]3)=[CH:13]1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 534015132-(6-(Trifluoromethyl)pyridin-2-yl)acetic acidHCID 668234705-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride

Produkt 1

HCID 668234781-[5-(4-Amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanoneAusbeute 39,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (150 mg, 0.443 mmol), [6-(trifluoromethyl)-2-pyridinyl]acetic acid (91 mg, 0.443 mmol), HATU (169 mg, 0.443 mmol), and DIEA (0.310 mL, 1.774 mmol) in N,N-Dimethylformamide (DMF) (3 mL) were stirred overnight at room temperature. LCMS analysis at this time indicated good conversion, so the reaction mixture was poured into water (10 mL) and stirred for 30 min. The resulting precipitate was collected by filtration, dried at the pump for an hour, adsorbed onto silica and purified by flash chromatography (0-10% MeOH in EtOAc) to afford 7-methyl-5-(1-{[6-(trifluoromethyl)-2-pyridinyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (80 mg, 39.9% yield) as a beige solid. LC-MS (ES) m/z=453 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.26 (t, J=8.34 Hz, 2H), 3.74 (s, 3H), 4.21 (s, 2H), 4.31 (t, J=8.46 Hz, 2H), 5.85-6.26 (m, 2H), 7.23 (d, J=8.34 Hz, 1H), 7.26 (s, 1H), 7.34 (s, 1H), 7.71 (d, J=7.83 Hz, 1H), 7.83 (d, J=7.58 Hz, 1H), 8.05-8.13 (m, 2H), 8.15 (s, 1H).

Aufarbeitung

  1. filtrationThe resulting precipitate was collected by filtration
  2. customdried at the pump for an hour
  3. custompurified by flash chromatography (0-10% MeOH in EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-261a87dc0bdf44099f55366c40ca5404
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598156B2

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