Dimethylformamide → 3-(4-Methyl-1H-imidazol-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide bis(trifluoroacetate)

HRID 1894871

Reaktionsgleichung

Reaktionsgleichung von HRID 1894871
[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:8]=[C:9]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=2)[C:10]([OH:12])=O)[CH:6]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)[O:30]N1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:53][C:54]1[CH:60]=[CH:59][C:57]([NH2:58])=[CH:56][C:55]=1[C:61]1[CH:69]=[C:68]2[C:64]([C:65]3[CH:73]=[N:72][CH:71]=[N:70][C:66]=3[NH:67]2)=[CH:63][CH:62]=1.CN([CH:77]=[O:78])C>>[F:17][C:16]([F:19])([F:18])[C:77]([OH:78])=[O:30].[F:17][C:16]([F:19])([F:18])[C:77]([OH:78])=[O:30].[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:8]=[C:9]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=2)[C:10]([NH:58][C:57]2[CH:59]=[CH:60][C:54]([CH3:53])=[C:55]([C:61]3[CH:69]=[C:68]4[C:64]([C:65]5[CH:73]=[N:72][CH:71]=[N:70][C:66]=5[NH:67]4)=[CH:63][CH:62]=3)[CH:56]=2)=[O:12])[CH:6]=1

Komponenten

6

Edukt 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 469002413-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acidHCID 690464994-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)aniline

Produkt 1

HCID 866219583-(4-Methyl-1H-imidazol-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide bis(trifluoroacetate)

Versuchsvorschrift

To 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acid (39 mg, 0.14 mmol, prepared according to WO2004005281) was added DMF (0.93 mL) followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (66.5 mg, 0.175 mmol) and N,N-diisopropylethylamine (DIPEA) (30.5 μL, 0.175 mmol). This solution was stirred at ambient temperature for 15 minutes, then 4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)aniline (40.0 mg, 0.146 mmol) was added. The reaction was held at ambient temperature until LCMS indicated complete reaction, typically 1-2 hours. The reaction was partitioned between water and EtOAc and the organic phase was washed with water and saturated aqueous NaCl, then dried (MgSO4) and evaporated to dryness to leave the crude product. This was purified by preparative LCMS to recover the product as a bis-TFA salt (60.3 mg, 55%). 1H NMR (400 MHz, DMSO): δ 13.0 (bs, 1H), 10.67 (s, 1H), 9.63 (s, 1H), 9.60 (s, 1H), 9.12 (s, 1H), 8.60 (s, 1H), 8.42 (m, 2H), 8.37 (d, 1H), 8.15 (s, 1H), 7.77 (m, 2H), 7.56 (s, 1H), 7.43 (dd, 1H), 7.37 (d, 1H), 2.33 (s, 3H), 2.26 (s, 3H). MS (EI) m/z=527 (M+H).

Aufarbeitung

  1. customwas held at ambient temperature until LCMS
  2. customreaction, typically 1-2 hours
  3. customThe reaction was partitioned between water and EtOAc
  4. washthe organic phase was washed with water and saturated aqueous NaCl
  5. dry with materialdried (MgSO4)
  6. customevaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-59020a56a9734ee08655758be62c85ca
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08513270B2

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