Diisopropylethylamine → 1-(2-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)-4-aza-1-azoniabicyclo-[2.2.2]octane chloride hydrochloride

HRID 83827노트

반응식

HRID 83827 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].[ClH:38].[Cl-].[NH2:40][CH2:41][CH2:42][N+:43]12[CH2:50][CH2:49][N:46]([CH2:47][CH2:48]1)[CH2:45][CH2:44]2.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>[ClH:1].[Cl-:38].[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)([CH3:20])[CH3:19])=[CH:16][N:17]=1)[C:5]([NH:40][CH2:41][CH2:42][N+:43]12[CH2:50][CH2:49][N:46]([CH2:45][CH2:44]1)[CH2:47][CH2:48]2)=[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 672347361-(2-Aminoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane chloride hydrochloride

생성물 1

HCID 867022211-(2-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)-4-aza-1-azoniabicyclo-[2.2.2]octane chloride hydrochloride수율 80.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a suspension of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (0.11 g, 0.19 mmol), 1-(2-aminoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane chloride hydrochloride (0.066 g, 2.5 mmol), and HATU (0.088 g, 0.23 mmol) in DMF (0.7 mL) was added DIPEA (0.2 mL, 1.16 mmol). The reaction was stirred for 2 h and purified by HPLC (MeCN/H2O, 10-99%, 0.05% TFA modifier). The product fractions were concentrated and then dissolved in THF (2 mL) and 2N solution of HCl in ether (2 mL). The mixture was filtered to afford the title compound (59 mg) as a white solid. 1H-NMR (DMSO-d6, 400 MHz) δ 9.67 (s, 1H), 7.84 (s, 1H), 7.84-7.76 (m, 2H), 7.27 (d, J=8.2 Hz, 1H), 7.01-6.97 (m, 2H), 6.50-6.43 (m, 4H), 4.22 (s, 2H), 3.86-3.71 (m, 10H), 3.67 (s, 3H), 3.53-3.49 (m, 6H), 1.49 (s, 6H); MS (ES): 700 [M]+.

후처리

  1. custompurified by HPLC (MeCN/H2O, 10-99%, 0.05% TFA modifier)
  2. concentrationThe product fractions were concentrated
  3. dissolutiondissolved in THF (2 mL)
  4. filtrationThe mixture was filtered

출처 및 근거

ORD 기록
ord-e6d6ec48b23b44bc8639a36d1c43f0e4
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846739B2

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