Acetic Acid → HCID 71014126、化合物

HRID 1430080ノート

反応式

HRID 1430080 の反応式
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([NH:14][C@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]1[OH:21])=[O:13])[CH:8]=[C:7]2[CH:22]=O.Cl.Cl.[Cl:26][C:27]1[CH:32]=[CH:31][N:30]=[C:29]([C:33]2([F:39])[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH:28]=1.C(O)(=O)C.C([BH3-])#N>ClCCCl.C(N(CC)CC)C.C(Cl)Cl>[Cl:26][C:27]1[CH:32]=[CH:31][N:30]=[C:29]([C:33]2([F:39])[CH2:34][CH2:35][N:36]([CH2:22][C:7]3[C:6]4[C:11](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=4)[N:10]=[C:9]([C:12]([NH:14][C@H:15]4[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]4[OH:21])=[O:13])[CH:8]=3)[CH2:37][CH2:38]2)[CH:28]=1

参加物

8

反応物 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 86726469HCID 86726469、化合物HCID 86726471HCID 86726471、化合物

生成物 1

HCID 71014126HCID 71014126、化合物

試薬・触媒・溶媒 3

HCID 8471Triethylamine触媒HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 8-fluoro-4-formyl-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide (C9) (0.080 g, 0.25 mmol) in DCE (3 mL) was 4-chloro-2-(4-fluoropiperidin-4-yl)pyridine dihydrochloride (C5) (0.080 g, 0.28 mmol) and triethylamine (6 drops). After 5 min, acetic acid (0.043 mL, 0.76 mmol) and MP-cyanoborohydride were added. The mixture was irradiated in a microwave reactor at 100° C. for 20 min, then diluted with CH2Cl2 and was washed with brine. The organic solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified via silica gel chromatography eluting with 0-5% methanol in dichloromethane to provide the title compound (Example C) as a white solid that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 515.0 for M+H+. 1H NMR (400 MHz, CDCl3) δ 8.44 (d, J=5.2 Hz, 1H), 8.38 (s, 1H), 8.29 (d, J=7.8 Hz, 1H), 8.17 (d, J=8.5 Hz, 1H), 7.60-7.55 (m, 2H), 7.47-7.42 (m, 1H), 7.22-7.20 (m, 1H), 4.03 (s, 2H), 3.94-3.86 (m, 1H), 3.63-3.56 (m, 1H), 3.42 (br s, 1H), 2.86-2.83 (m, 2H), 2.62-2.56 (m, 2H), 2.47-2.30 (m, 2H), 2.17-2.11 (m, 2H), 1.89-1.78 (m, 4H), 1.56-1.31 (m, 4H).

後処理

  1. customThe mixture was irradiated in a microwave reactor at 100° C. for 20 min
  2. washwas washed with brine
  3. dry with materialThe organic solution was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified via silica gel chromatography
  7. washeluting with 0-5% methanol in dichloromethane

出典と根拠

ORDレコード
ord-2b03cb4ca50e48338d4ec91d3797ccbd
出典データセット
uspto-grants-2015_01
特許番号
US08940765B2

反応ノート

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