2,6-Lutidine → {[6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoylamino]methyl}-phosphonic acid

HRID 33016노트

반응식

HRID 33016 반응식
C([O:3][P:4]([CH2:9][NH:10][C:11](=[O:38])[CH2:12][CH2:13][C:14]([CH3:37])=[CH:15][CH2:16][C:17]1[C:18]([O:30]CC[Si](C)(C)C)=[C:19]2[C:23](=[C:24]([CH3:28])[C:25]=1[O:26][CH3:27])[CH2:22][O:21][C:20]2=[O:29])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.N1C(C)=CC=CC=1C>C(#N)C>[OH:30][C:18]1[C:17]([CH2:16][CH:15]=[C:14]([CH3:37])[CH2:13][CH2:12][C:11]([NH:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[O:38])=[C:25]([O:26][CH3:27])[C:24]([CH3:28])=[C:23]2[C:19]=1[C:20](=[O:29])[O:21][CH2:22]2

참가 물질

5

반응물 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 76541034({-6-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoylamino}-methyl)-phosphonic acid diethyl ester

생성물 1

HCID 67010439{[6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoylamino]methyl}-phosphonic acid수율 9%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a solution of ({6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoylamino}-methyl)-phosphonic acid diethyl ester (40 mg, 0.07 mmol) in acetonitrile (1 mL) was added TMSBr (91 μL, 0.7 mmol) followed by 2,6-lutidine (81.5 μL, 0.7 mmol). The reaction was allowed to proceed overnight when it was completed as judged by LCMS. The reaction mixture was quenched with MeOH and concentrated to dryness. The residue was purified by preparative reverse-phase HPLC to afford 2.6 mg (9%) of desired product as a white solid. 1H NMR (300 MHz, CD3OD) δ 1.67 (s, 3H), 2.17 (m, 5H), 2.30-2.46 (m, 2H), 2.80-2.86 (m, 2H), 3.55 (m, 2H), 3.82 (s, 3H), 5.26 (s, 3H) ppm; 31P (121.4 MHz, CD3OD) δ 10.27 ppm; MS (m/z) 412 [M−H]−, 414 [M+H]+.

후처리

  1. customThe reaction mixture was quenched with MeOH
  2. concentrationconcentrated to dryness
  3. customThe residue was purified by preparative reverse-phase HPLC

출처 및 근거

ORD 기록
ord-bd794bf198c94e3c880268830c76c99a
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427636B2

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