Selectfluor → Tak-733

HRID 1260446ノート

反応式

HRID 1260446 の反応式
[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

参加物

5

反応物 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

生成物 1

HCID 24963252Tak-733収率 33%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 6342Acetonitrile溶媒

実験手順

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 C17H15F21N4O4, 505. found, 505.

後処理

  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)

出典と根拠

ORDレコード
ord-50dfa339ab97454e995dd7c0571c99d3
出典データセット
uspto-grants-2013_06
特許番号
US08470837B2

反応ノート

読み込み中…