Selectfluor → (s)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3h,8h)-dione

HRID 1660899Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1660899
[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 24965731(S)-3-(2,3-Dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Produkt 1

HCID 24963251(s)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3h,8h)-dioneAusbeute 25,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of (S)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 5) (1.25 g, 2.58 mmol, 1 eq) in DMF (26 mL) was added a mixture of Selectfluor (1.187 g, 3.35 mmol, 1.3 eq) in acetonitrile (26 mL). The reaction mixture was irradiated with microwave at 82° C. for 10 minutes and filtered. The filtrate was purified by preparatory LC/MS (30-55% CH3CN in H2O) to give (S)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 19) as an off-white solid (331 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.36-3.42 (m, 1H) 3.42-3.51 (m, 1H) 3.59 (s, 3H) 3.63-3.72 (m, 1H) 3.73-3.81 (m, 1H) 4.32 (dd, J=13.14, 3.03 Hz, 1H) 4.79 (br. s., 1H) 5.10 (br. s., 1H) 6.98 (td, J=8.46, 5.31 Hz, 1H) 7.52 (dd, J=8.46, 1.14 Hz, 1H) 7.68 (dd, J=10.36, 1.77 Hz, 1H) 8.51 (s, 1H) 10.24 (d, J=2.27 Hz, 1H). [M+H] calc'd for C17H15F2IN4O4, 505; found, 505.

Aufarbeitung

  1. customThe reaction mixture was irradiated with microwave at 82° C. for 10 minutes
  2. filtrationfiltered
  3. customThe filtrate was purified by preparatory LC/MS (30-55% CH3CN in H2O)

Quellen und Nachweise

ORD-Eintrag
ord-236092ae6cf147238d9cf00bdddb1313
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030317B2

Notizen zur Reaktion

Wird geladen…