Diisopropylethylamine → 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-(pyridin-2-yl)-3,4-dihydro-2,6-naphthyridin-2(1H)-yl)ethane-1,2-dione

HRID 885076ノート

反応式

HRID 885076 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH3:14])=[N:10]2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([OH:21])=O)[C:4]=12.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]1[N:38]=[CH:37][CH:36]=[C:35]2[C:30]=1[CH2:31][CH2:32][NH:33][CH2:34]2.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH3:14])=[N:10]2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([N:33]3[CH2:32][CH2:31][C:30]4[C:35](=[CH:36][CH:37]=[N:38][C:29]=4[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=4)[CH2:34]3)=[O:21])[C:4]=12

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 580260655-(Pyridin-2-yl)-1,2,3,4-tetrahydro-2,6-naphthyridineHCID 596815922-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid

生成物 1

HCID 445557891-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-(pyridin-2-yl)-3,4-dihydro-2,6-naphthyridin-2(1H)-yl)ethane-1,2-dione

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of 2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (0.062 g, 0.205 mmol), 5-(pyridin-2-yl)-1,2,3,4-tetrahydro-2,6-naphthyridine (0.062 g, 0.205 mmol), and TBTU (0.086 g, 0.267 mmol) in DMF (3 mL) was added Hunig's Base (0.2 mL, 1.145 mmol). The mixture was stirred at rt for 15.75 h and quenched with 5 mL of water and concentrated under reduced pressure. The residue was dissolved in DMF, filtered through a plug of glass wool, and was purified by prep HPLC. The fractions containing the expected product were combined and concentrated. The residue was dissolved in dichloromethane and washed with sat. aq. NaHCO3. The organic layer was dried with MgSO4, was filtered, and was concentrated under reduced pressure to give the expected product as a light pink solid. The compound was further purified using BIOTAGE® flash chromatography with a 0-6% MeOH in dichloromethane gradient. The expected product, 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-(pyridin-2-yl)-3,4-dihydro-2,6-naphthyridin-2(1H)-yl)ethane-1,2-dione, 1.4 H2O (0.041 g, 0.077 mmol, 37.7% yield), was isolated as an off-white solid. LC/MS: m/z 495.19 (M+H)+, 0.922 min (method 4). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.04 (br. s., 1H) 9.07-9.12 (m, 1H) 8.48-8.71 (m, 2H) 8.20-8.26 (m, 1H) 7.79-7.90 (m, 2H) 7.71-7.74 (m, 1H) 7.27-7.37 (m, 1H) 7.00-7.23 (m, 1H) 4.80-5.00 (m, 2H) 3.75-3.96 (m, 5H) 3.22-3.36 (m, 2H) 2.50-2.61 (m, 3H) 1.57 (s, 3H).

後処理

  1. customquenched with 5 mL of water
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in DMF
  4. filtrationfiltered through a plug of glass wool
  5. customwas purified by prep HPLC
  6. additionThe fractions containing the expected product
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in dichloromethane
  9. washwashed with sat. aq. NaHCO3
  10. dry with materialThe organic layer was dried with MgSO4
  11. filtrationwas filtered
  12. concentrationwas concentrated under reduced pressure

出典と根拠

ORDレコード
ord-f5a02ba561624bf49c1e516ae86b42e3
出典データセット
uspto-grants-2012_08
特許番号
US08242124B2

反応ノート

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