Acetic Acid → HCID 136248870、化合物

HRID 922410ノート

反応式

HRID 922410 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2[NH:23][C:22](=[O:24])[C:21]3[C:16](=[CH:17][C:18]([O:27][CH3:28])=[CH:19][C:20]=3[O:25][CH3:26])[N:15]=2)[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=1.[CH3:29][C:30]([CH3:32])=O.C([O-])(=O)C.[Na+].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2[NH:23][C:22](=[O:24])[C:21]3[C:16](=[CH:17][C:18]([O:27][CH3:28])=[CH:19][C:20]=3[O:25][CH3:26])[N:15]=2)[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH:30]([CH3:32])[CH3:29])[CH2:10][CH2:9]2)[CH:7]=1

参加物

7

反応物 5

HCID 176Acetic AcidHCID 180AcetoneHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 136248869HCID 136248869、化合物

生成物 1

HCID 136248870HCID 136248870、化合物収率 18%

試薬・触媒・溶媒 1

HCID 22134543HCID 22134543、化合物溶媒

実験手順

To a solution of 2-(3-chloro-5-(piperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (Example 31, 0.054 g, 0.14 mmol), acetone (0.060 g, 1.4 mmol), sodium acetate (0.023 g, 0.27 mmol), and acetic acid (0.16 g, 2.7 mmol) in 1,2-dichloroethane/methanol (5/5 mL) was added sodium triacetoxyborohydride (0.56 g, 2.7 mmol). The mixture was stirred at room temperature for 16 h and then concentrated. The residue was purified by silica gel chromatography eluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2. This material was further purified by reverse phase HPLC eluting with 10% to 90% CH3CN in H2O with 0.1% TFA. The product fractions were concentrated and the residue was dissolved in acetonitrile and water. The mixture was basified with concentrated NH4OH and concentrated. The residue was purified by reverse phase HPLC eluting with 10% to 90% CH3CN in H2O without TFA to afford the title compound (0.011 g, 18%) as an off-white solid: 1H NMR (500 MHz, CD3OD) δ 7.52 (s, 1H), 7.49 (d, J=1.5 Hz, 1H), 7.18 (t, J=1.5 Hz, 1H), 6.82 (d, J=2.5 Hz, 1H), 6.59 (d, J=2.5 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.35-3.60 (br s, 4H), 2.85-3.15 (br s, 4H), 1.25-1.40 (br s, 1H), 1.23 (d, J=6.5 Hz, 6H); ESI MS m/z 443 [M+H]+.

後処理

  1. concentrationconcentrated
  2. customThe residue was purified by silica gel chromatography
  3. washeluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2
  4. customThis material was further purified by reverse phase HPLC
  5. washeluting with 10% to 90% CH3CN in H2O with 0.1% TFA
  6. concentrationThe product fractions were concentrated
  7. dissolutionthe residue was dissolved in acetonitrile
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC
  10. washeluting with 10% to 90% CH3CN in H2O without TFA

出典と根拠

ORDレコード
ord-69b40557294345aebd94aca6cb29e7ab
出典データセット
uspto-grants-2016_03
特許番号
US09278940B2

反応ノート

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