Selectfluor → Tak-733

HRID 2067755Notes

Reaction equation

HRID 2067755 reaction equation
[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

Participants

5

Reactant 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

Product 1

HCID 24963252Tak-733Yield 33%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Procedure

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, 1 H) 3.43-3.50 (m, 1 H) 3.58 (s, 3 H) 3.61-3.72 (m, 1 H) 3.72-3.82 (m, 1 H) 4.27-4.37 (m, 1 H) 4.78-4.87 (m, 1 H) 5.14 (d, J=5.81 Hz, 1 H) 6.93-7.03 (m, 1 H) 7.53 (d, J=8.84 Hz, 1 H) 7.65-7.74 (m, 1 H) 8.52 (s, 1 H) 10.25 (d, J=1.01 Hz, 1 H). [M+H] calc'd for C17H15F21N4O4, 505; found, 505.

Workup

  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)

Sources & evidence

ORD record
ord-01644f4055f544eda60a277ca2061cbb
Source dataset
uspto-grants-2012_10
Patent number
US08293901B2

Reaction notes

Loading…