Tris(trimethylsilyl) phosphite → 5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbonylphosphonic acid

HRID 2167660

반응식

HRID 2167660 반응식
[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([CH:27]=[O:28])=[CH:26][C:4]=2[N:3]=1.[P:29]([O:40][Si](C)(C)C)([O:35][Si](C)(C)C)[O:30][Si](C)(C)C>C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([C:27]([P:29](=[O:30])([OH:40])[OH:35])=[O:28])=[CH:26][C:4]=2[N:3]=1

참가 물질

4

반응물 2

HCID 137213Tris(trimethylsilyl) phosphiteHCID 581665185-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde

생성물 1

HCID 498385115-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbonylphosphonic acid

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
80 °C

실험 절차

To a stirred suspension of 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde (2-2) (Example 9—Step 1) (1.0 equiv.) in toluene (0.27 M) was added tris(trimethylsilyl) phosphite (1.0 equiv.). The reaction was stirred at 80° C. for 60 minutes, then solvents were removed, and the resulting residue was taken up in DMSO (0.27 M), and IBX (1.5 equiv.) was added. The reaction was stirred at room temperature for 2.5 hour, and was filtered and directly purified on RP-HPLC using a C18 column, eluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient. The fractions containing the product were combined and concentrated in vacuo to give 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbonylphosphonic acid (14) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 9.84 (s, 1H), 9.35 (s, 1H), 9.09 (s, 1 H), 8.89 (s, 1 H), 8.76 (d, 1H, J=8.4 Hz), 8.60 (s, 1H), 8.19 (d, 1H, J=8.8 Hz), 7.04 (d, J=8.8 Hz, 1H), 6.70 (d, 1H, J=2.8 Hz), 6.62 (dd, 1H, J=2.8, 8.4 Hz), 3.64 (s, 3H), 3.15-3.09 (m, 2H), 2.97-2.91 (m, 2H), 2.23 (s, 3H). LRMS [M+H]=452.1

후처리

  1. customsolvents were removed
  2. additionIBX (1.5 equiv.) was added
  3. stirringThe reaction was stirred at room temperature for 2.5 hour
  4. filtrationwas filtered
  5. customdirectly purified on RP-HPLC
  6. washeluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient
  7. additionThe fractions containing the product
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-97ced71f170d495caa500d1cb43e93f2
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045470B2

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