Acetic Acid → HCID 71014126, 화합물

HRID 1430080노트

반응식

HRID 1430080 반응식
[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

참가 물질

8

반응물 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 86726469HCID 86726469, 화합물HCID 86726471HCID 86726471, 화합물

생성물 1

HCID 71014126HCID 71014126, 화합물

시약·촉매·용매 3

HCID 8471Triethylamine촉매HCID 111,2-Dichloroethane용매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2b03cb4ca50e48338d4ec91d3797ccbd
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940765B2

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