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Dimethylformamide → (1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3h-imidazol-4-yl}-6-methyl-6,7-dihydro-5h-dibenzo[c,e]azepin-3-yl)-1h-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 417406
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인쇄 미리보기

반응식

HRID 417406 반응식
[CH3:1][O:2][C:3](=[O:5])[NH2:4].[NH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11]1[NH:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]3[C:25]4[CH:26]=[CH:27][C:28]([C:30]5[NH:31][C:32]([CH:35]6[CH2:39][CH2:38][CH2:37][NH:36]6)=[N:33][CH:34]=5)=[CH:29][C:24]=4[CH2:23][N:22]([CH3:40])[CH2:21][C:20]=3[CH:41]=2)=[CH:13][N:12]=1.[CH3:42][O:43][C:44]([NH:46][C@H:47]([C:51]([OH:53])=O)[CH:48]([CH3:50])[CH3:49])=[O:45].CN(C(ON1N=NC2[CH:65]=[CH:66][CH:67]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:78](N(C(C)C)CC)(C)C.CN([CH:90]=[O:91])C>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:5])[NH:4][CH:78]([C:90]([N:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11]1[NH:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]3[C:25]4[CH:26]=[CH:27][C:28]([C:30]5[NH:31][C:32]([CH:35]6[CH2:39][CH2:38][CH2:37][N:36]6[C:51](=[O:53])[CH:47]([NH:46][C:44]([O:43][CH3:42])=[O:45])[CH:48]([CH3:49])[CH3:50])=[N:33][CH:34]=5)=[CH:29][C:24]=4[CH2:23][N:22]([CH3:40])[CH2:21][C:20]=3[CH:41]=2)=[CH:13][N:12]=1)=[O:91])[CH:66]([CH3:65])[CH3:67]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 6

HCID 6228DimethylformamideHCID 11722Methyl CarbamateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid
HCID 66620578
3,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine

생성물 1

HCID 66620472(1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3h-imidazol-4-yl}-6-methyl-6,7-dihydro-5h-dibenzo[c,e]azepin-3-yl)-1h-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester: To the solution of 3,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine (25 mg, 0.035 mmol) and MeOCO-Val-OH (13 mg, 0.074 mmol) in DMF (1.2 ml) was added HATU (28 mg, 0.074 mmol), followed by diisopropylethylamine (61 μl, 0.35 mmol). The mixture was stirred for 90 minutes and was diluted with EtOAc. The organic phase was washed with 1 N NaOH solution, water, and brine, and was dried with sodium sulfate. Concentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O) gave (1-{2-[5-(9-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (24 mg). m/z: 794.3 (M+H)+, 397.8 (M+2H)+/2. 1H NMR (CD3OD, 300 MHz) δ 8.0-7.9 (8H, m), 5.27 (2H, m), 4.3-4.2 (2H, m), 4.2-3.8 (8H, m), 3.66 (6H, s), 3.08 (3H, s), 2.7-2.5 (2H, m), 2.4-1.9 (8H, m), 0.94-0.90 (12H, m).

후처리

  1. washThe organic phase was washed with 1 N NaOH solution, water, and brine
  2. dry with materialwas dried with sodium sulfate
  3. concentrationConcentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O)

출처 및 근거

ORD 기록
ord-28c1322102bc44f9a1748860f6cb0583
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08088368B2

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