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

HRID 2374096노트

반응식

HRID 2374096 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-280e17c1636f4aa0a1a0497f897e61cd
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07459562B2

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