Diisopropylethylamine → 4-(4-(1-Benzyl-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide

HRID 2237316ノート

反応式

HRID 2237316 の反応式
[CH2:1]([N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([OH:16])=O)[C:9]1=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:18][C:19]1[CH:34]=[CH:33][C:22]([O:23][C:24]2[CH:29]=[CH:28][N:27]=[C:26]([C:30]([NH2:32])=[O:31])[CH:25]=2)=[C:21]([F:35])[CH:20]=1.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>[CH2:1]([N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:18][C:19]2[CH:34]=[CH:33][C:22]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([C:30]([NH2:32])=[O:31])[CH:25]=3)=[C:21]([F:35])[CH:20]=2)=[O:16])[C:9]1=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27640211-Benzyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 231532054-(4-Amino-2-fluorophenoxy)picolinamide

生成物 1

HCID 598529484-(4-(1-Benzyl-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide収率 69.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A homogeneous solution of 1-benzyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid (0.10 g, 0.41 mmol, 1.0 eq), 4-(4-amino-2-fluorophenoxy)picolinamide (0.10 g, 0.41 mmol, 1.0 eq) and TBTU (0.17 g, 0.45 mmol, 1.1 eq) in DMF (2 mL) was treated with DIPEA (0.18 mL, 1.0 mmol, 2.5 eq) at room temperature and the reaction mixture was stirred for 12 h. The reaction mixture was quenched with 10% aqueous LiCl (15 mL) and the resulting solution was extracted with ethyl acetate (4×40 mL). The combined organic extracts were washed with 10% aqueous LiCl (4×50 mL), dried (Na2SO4), filtered and the filtrate concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, eluting with ethyl acetate) to afford the product (0.13 g, 67%) as a solid. 1H NMR (DMSO-d6) δ 12.26 (s, 1H), 8.49-8.56 (m, 2H), 8.33-8.36 (m, 1H), 8.15 (br m, 1H), 8.03-8.07 (m, 1H), 7.74-7.75 (m, 1H), 7.51-7.54 (m, 1H), 7.41-7.46 (m, 4H), 7.20-7.24 (m, 3H), 6.71 (dd, 1H, J=6.89 Hz), 5.32 (s, 2H) HRMS(ESI+), Calcd.: 477.1374, found: 477.1378.

後処理

  1. customThe reaction mixture was quenched with 10% aqueous LiCl (15 mL)
  2. extractionthe resulting solution was extracted with ethyl acetate (4×40 mL)
  3. washThe combined organic extracts were washed with 10% aqueous LiCl (4×50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe residue was purified by flash column chromatography (SiO2, eluting with ethyl acetate)

出典と根拠

ORDレコード
ord-e205384ad4784dbb9f657807eba55dcd
出典データセット
uspto-grants-2010_05
特許番号
US07714138B2

反応ノート

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