Selectfluor → Tak-733

HRID 1660898Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1660898
[OH:1][C@@H:2]([CH2:26][OH:27])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=3[F:25])=[CH:12][C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1.[B-](F)(F)(F)[F:29].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>CN(C=O)C.C(#N)C>[OH:1][C@@H:2]([CH2:26][OH:27])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=3[F:25])=[C:12]([F:29])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1

Komponenten

5

Edukt 2

HCID 2724933SelectfluorHCID 53323815(r)-3-(2,3-Dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3h,8h)-dione

Produkt 1

HCID 24963252Tak-733Ausbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of (R)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 6) (1 g, 2.06 mmol, 1 eq) in DMF (19 mL) was added dropwise a mixture of Selectfluor (801 mg, 2.26 mmol, 1.1 eq) in acetonitrile (9 mL) and DMF (5 mL) at ambient temperature while stirring under nitrogen. The reaction mixture was stirred for 10 minutes at ambient temperature and filtered. The filtrate was purified by preparatory LC/MS (30-55% CH3CN in H2O) to give (R)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 18) as an off-white solid. The recovered starting material was subjected to the same reaction conditions to produce a second crop of product. The total yield of product was 347 mg (33% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.36-3.40 (m, 1H) 3.43-3.50 (m, 1H) 3.58 (s, 3H) 3.61-3.72 (m, 1H) 3.72-3.82 (m, 1H) 4.27-4.37 (m, 1H) 4.78-4.87 (m, 1H) 5.14 (d, J=5.81 Hz, 1H) 6.93-7.03 (m, 1H) 7.53 (d, J=8.84 Hz, 1H) 7.65-7.74 (m, 1H) 8.52 (s, 1H) 10.25 (d, J=1.01 Hz, 1H). [M+H] calc'd for C17H15F2IN4O4, 505; found, 505.

Aufarbeitung

  1. stirringThe reaction mixture was stirred for 10 minutes at ambient temperature
  2. filtrationfiltered
  3. customThe filtrate was purified by preparatory LC/MS (30-55% CH3CN in H2O)

Quellen und Nachweise

ORD-Eintrag
ord-58d015651acd4fe490d80720ef94efc1
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030317B2

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