1,2-Dichloroethane → N-(2-hydroxyethyl)-6-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinamide

HRID 58108ノート

反応式

HRID 58108 の反応式
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][C:3]=1[C:11]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[C:16]2[C:12]=1[CH:13]=[N:14][NH:15]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:38][CH2:39][CH2:40][OH:41].C(N(C(C)C)C(C)C)C>CN(C=O)C.CCOC(C)=O>[OH:41][CH2:40][CH2:39][NH:38][C:8](=[O:10])[C:6]1[CH:5]=[CH:4][C:3]([C:11]2[CH:19]=[C:18]([C:20]([F:23])([F:21])[F:22])[CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][NH:15]3)=[C:2]([CH3:1])[N:7]=1

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 700EthanolamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 897833556-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinic acid

生成物 1

HCID 89782824N-(2-hydroxyethyl)-6-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinamide収率 36.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To 6-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinic acid (1.6 g, 4.98 mmol) in DMF (20 mL) were added HOBt (0.942 g, 6.97 mmol), EDC (1.432 g, 7.47 mmol), 2-aminoethanol (0.913 g, 14.94 mmol), followed by N-ethyl-N-isopropylpropan-2-amine (4.34 mL, 24.90 mmol). The reaction mixture was stirred for 16 hours at room temperature, was subsequently diluted with EtOAc and was washed with brine. Volatiles were evaporated from the organic phase and the residue was purified by CombiFlash® chromatography, eluting with a gradient of 0-20% MeOH in DCM. The product-containing fractions were combined and concentrated in vacuo to give the title compound as a white solid (0.658 g, 36.3%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3H), 3.44 (q, J=5.98 Hz, 2H), 3.57 (t, J=5.94 Hz, 2H), 7.38-7.44 (m, 1H), 7.90-8.07 (m, 4H), 8.70 (t, J=5.81 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C17H15F3N4O2, 365.1. found 365.2.

後処理

  1. washwas washed with brine
  2. customVolatiles were evaporated from the organic phase
  3. customthe residue was purified by CombiFlash® chromatography
  4. washeluting with a gradient of 0-20% MeOH in DCM
  5. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-d8e84ccb75fa4262a6068ee19592e58f
出典データセット
uspto-grants-2016_09
特許番号
US09434743B2

反応ノート

読み込み中…