Triethylamine → 4-{2-[(Morpholine-4-carbonyl)-amino]-2-phenyl-acetyl}-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

HRID 2075779노트

반응식

HRID 2075779 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH2:38])[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1.[N:42]1([C:48](Cl)=[O:49])[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C(N(CC)CC)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH:38][C:48]([N:42]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)=[O:49])[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 848104-Morpholinecarbonyl chlorideHCID 1363466894-(2-Amino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

생성물 1

HCID 1363466924-{2-[(Morpholine-4-carbonyl)-amino]-2-phenyl-acetyl}-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of compound 9D in anhydrous CH2Cl2 were slowly added 4-morpholinecarbonyl chloride (14D, 1.2 eq) and triethylamine (1.5 eq), successively. The reaction mixture was stirred at rt overnight. It was concentrated to small volume and purified with silica column chromatography eluting with dichloromethane/EtOAc to give the title compound (15D) which was recrystallized from hexanes/acetone to provide compound 15D as white powder in ˜60% yield. 1H NMR (CDCl3, 500 MHz) δ 10.67 (s, 1H), 8.93 (s, 1H), 8.70 (s, 1H), 7.93 (d, 2H, J=7.5 Hz), 7.63 (s, 1H), 7.55 (d, 2H, J=7.5 Hz), 7.45 (s, 5H), 7.19 (d, 1H, J=8.0 Hz), 6.97 (d, 1H, J=8.0 Hz), 5.60 (d, 1H, J=6.5 Hz), 5.28 (s, 1H), 5.18 (d, 1H, J=6.5 Hz), 4.86 (d, 1H, J=12.0 Hz), 3.97 (s, 3H), 3.83 (m, 4H), 3.70 (br s, 4H), 3.45 (m, 2H), 3.37 (m, 2H), 3.17 (m, 1H). LCMS (ESI) m/z 705.43 (MNa+), 683.39 (MH+). HPLC: tR=4.95 min.

후처리

  1. concentrationIt was concentrated to small volume
  2. custompurified with silica column chromatography
  3. washeluting with dichloromethane/EtOAc

출처 및 근거

ORD 기록
ord-3edd05f06d294d3492afe059b3173096
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07923004B2

반응 노트

불러오는 중…