Diisopropylethylamine → 2-[6-chloro-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-N-[2-(1-trityl-1H-imidazol-4-yl)-benzyl]-acetamide

HRID 1795303노트

반응식

HRID 1795303 반응식
[Cl:1][C:2]1[N:7]([CH2:8][C:9]([OH:11])=O)[C:6](=[O:12])[C:5]([NH:13][CH2:14][C:15]([F:23])([F:22])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[N:4][CH:3]=1.C(O)(=O)C(O)=O.[C:30]([N:49]1[CH:53]=[C:52]([C:54]2[CH:61]=[CH:60][CH:59]=[CH:58][C:55]=2[CH2:56][NH2:57])[N:51]=[CH:50]1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.O>[Cl:1][C:2]1[N:7]([CH2:8][C:9]([NH:57][CH2:56][C:55]2[CH:58]=[CH:59][CH:60]=[CH:61][C:54]=2[C:52]2[N:51]=[CH:50][N:49]([C:30]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:53]=2)=[O:11])[C:6](=[O:12])[C:5]([NH:13][CH2:14][C:15]([F:23])([F:22])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[N:4][CH:3]=1

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10936874[6-Chloro-3-(2.2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin 1-yl]-acetic AcidHCID 221851452-(1-Trityl-1h-imidazol-4-yl)-benzylamine oxalate salt

생성물 1

HCID 221851502-[6-chloro-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-N-[2-(1-trityl-1H-imidazol-4-yl)-benzyl]-acetamide

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A solution of [6-chloro-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid (25 mg, 0.058 mmol, preparation described in example 17), 2-(1-trityl-1H-imidazol-4-yl)-benzylamine oxalate salt (35 mg, 0.070 mmol, preparation described in example 2), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (17 mg, 0.087 mmol), 1-hydroxy-7-azabenzotriazole (12 mg, 0.087 mmol) and diisopropylethylamine (40 ul, 0.23 mmol) in N,N-dimethylformamide (1 ml) was stirred at room temperature overnight. Water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with brine. Drying and solvent evaporation gave 2-[6-chloro-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-N-[2-(1-trityl-1H-imidazol-4-yl)-benzyl]-acetamide; 1H NMR (CDCl3, 300 MHz) δ 9.11 (m, 1H), 8.65 (d, 1H, J=4.6 Hz), 8.02 (s, 1H), 7.80 (m, 1H), 7.61 (m, 1H), 7.47 (m, 1H), 7.38–7.15 (m, 18H), 6.99 (d, 1H, J=1.2 Hz), 6.78 (s, 1H), 6.36 (m, 1H), 4.78 (s, 2H), 4.43 (d, 2H, J=6.4 Hz), 4.14 (m, 2H).

후처리

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. customDrying
  4. customsolvent evaporation

출처 및 근거

ORD 기록
ord-5a37467e75204b2190ca767a59b36088
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07026324B2

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