Diisopropylethylamine → HCID 178489994, 화합물

HRID 1627264노트

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HRID 1627264 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:20])[CH3:19])=[CH:16][N:17]=1)[C:5](O)=[O:6].[NH2:38][C@@H:39]([CH2:47][CH2:48][CH2:49][NH:50][C:51]([NH2:53])=[NH:52])[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:19])[CH3:20])=[CH:16][N:17]=1)[C:5]([NH:38][C@@H:39]([CH2:47][CH2:48][CH2:49][NH:50][C:51]([NH2:53])=[NH:52])[C:40]([O:42][C:43]([CH3:46])([CH3:44])[CH3:45])=[O:41])=[O:6]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 667398303-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acidHCID 178451198HCID 178451198, 화합물

생성물 1

HCID 178489994HCID 178489994, 화합물수율 91%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (0.96 g, 1.70 mmol) and (S)-tert-butyl 2-amino-5-guanidinopentanoate (0.54 g, 1.79 mmol) in DMF (4 mL) at 0° C. was added HATU (0.69 g, 1.79 mmol) and DIPEA (0.82 mL, 5.27 mmol). The reaction was stirred at room temperature for 1 h, quenched with satd NaHCO3 and diluted with EtOAc. The mixture was washed with water (10 mL), brine (10 mL) and dried with Na2SO4. The residue was purified by column chromatography (silica, MeOH/DCM) to afford (S)-tert-butyl 2-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)-5-guanidinopentanoate (1.2 g) as a white solid. The solids were dissolved in 4N HCl in dioxane (8 mL) and stirred for 3 h. The reaction was concentrated and purified by chromatography (silica, MeOH/DCM) to yield the title compound (380 mg) as a white solid. 1H-NMR (DMSO-d6, 400 MHz) δ 8.84 (d, J=7.6 Hz, 1H), 7.81 (s, 1H), 7.64-7.61 (m, 1H), 7.46-7.43 (m, 1H), 7.21 (d, J=8.30 Hz, 1H), 7.18 (s, 1H), 7.01-6.93 (m, 2H), 6.61-6.57 (m, 1H), 6.54-6.49 (m, 3H), 4.37-4.31 (m, 1H), 4.07 (s, 2H), 3.68 (s, 3H), 3.15-3.11 (m, 2H), 1.88-1.70 (m, 2H), 1.61-1.54 (m, 2H), 1.47-1.46 (m, 6H), 1.42 (s, 9H); MS (EI) m/z 719 [MH]+.

후처리

  1. customquenched with satd NaHCO3
  2. additiondiluted with EtOAc
  3. washThe mixture was washed with water (10 mL), brine (10 mL)
  4. dry with materialdried with Na2SO4
  5. customThe residue was purified by column chromatography (silica, MeOH/DCM)

출처 및 근거

ORD 기록
ord-dc242b52150f412a98b7e783207b6272
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785488B2

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