1,2-Dichloroethane → N-(4-chloro-3-(trifluoro methyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide

HRID 576220노트

반응식

HRID 576220 반응식
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[CH2:13]([O:15][C:16]1[C:21](=[O:22])[NH:20][CH:19]=[C:18]([C:23]2[CH:28]=[CH:27][C:26]([CH2:29][C:30](O)=[O:31])=[C:25]([F:33])[CH:24]=2)[CH:17]=1)[CH3:14].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>CN(C=O)C>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:30](=[O:31])[CH2:29][C:26]2[CH:27]=[CH:28][C:23]([C:18]3[CH:17]=[C:16]([O:15][CH2:13][CH3:14])[C:21](=[O:22])[NH:20][CH:19]=3)=[CH:24][C:25]=2[F:33])=[CH:4][C:3]=1[C:9]([F:10])([F:11])[F:12]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 675744-Chloro-3-(trifluoromethyl)anilineHCID 757711-HydroxybenzotriazoleHCID 904154342-(4-(5-Ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acid

생성물 1

HCID 78426744N-(4-chloro-3-(trifluoro methyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide수율 23.6%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
50 °C

실험 절차

A suspension of 4-chloro-3-(trifluoromethyl)aniline (20.14 mg, 0.103 mmol) in DMF (8 mL) was added to a solution of 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acid (30 mg, 0.103 mmol) in DMF (8 mL). HOBt (23.66 mg, 0.154 mmol), EDC (29.6 mg, 0.154 mmol) and Et3N (0.043 mL, 0.309 mmol) were added and the mixture was stirred at 50° C. for 8 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition) to yield a white solid of N-(4-chloro-3-(trifluoro methyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide (11.39 mg, 0.024 mmol, 23.6% yield). TLC (DCM/MeOH=10:1, Rf=0.6): 1H NMR (400 MHz, CD3OD) δ: 8.10 (s, 1H), 7.79 (d, J=8.82 Hz, 1H), 7.53 (d, J=8.82 Hz, 1H), 7.37-7.44 (m, 1H), 7.26-7.37 (m, 3H), 7.23 (d, J=1.98 Hz, 1H), 4.12 (q, J=7.06 Hz, 2H), 3.80 (s, 2H), 1.46 (t, J=6.95 Hz, 3H); ES-LCMS m/z 469.1 (M+H).

후처리

  1. concentrationThen the solution was concentrated
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition)

출처 및 근거

ORD 기록
ord-281b6c31ae4e45e1a04062ca37c9534d
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09035063B2

반응 노트

불러오는 중…