Diisopropylethylamine → 3-((2-(3-Chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)dimethylammonio)-propane-1-sulfonate

HRID 83828노트

반응식

HRID 83828 반응식
[NH2:1][CH2:2][CH2:3][N+:4]([CH3:13])([CH3:12])[CH2:5][CH2:6][CH2:7][S:8]([O-:11])(=[O:10])=[O:9].[Cl:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([F:50])[C:23]=1[CH2:24][S:25][C:26]1[N:27]([C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=2)[C:28]([C:31]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([O:41][CH3:42])[CH:35]=2)([CH3:33])[CH3:32])=[CH:29][N:30]=1)[C:18](O)=[O:19].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([F:50])[C:23]=1[CH2:24][S:25][C:26]1[N:27]([C:43]2[CH:44]=[CH:45][C:46]([F:49])=[CH:47][CH:48]=2)[C:28]([C:31]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([O:41][CH3:42])[CH:35]=2)([CH3:33])[CH3:32])=[CH:29][N:30]=1)[C:18]([NH:1][CH2:2][CH2:3][N+:4]([CH3:12])([CH3:13])[CH2:5][CH2:6][CH2:7][S:8]([O-:11])(=[O:9])=[O:10])=[O:19]

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 56969970HCID 56969970, 화합물HCID 667398303-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid

생성물 1

HCID 532523893-((2-(3-Chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)dimethylammonio)-propane-1-sulfonate수율 63.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of tert-butyl 2-(dimethylamino)ethylcarbamate (1.8 g, 7.98 mmol) and 1,3-sultone (1.07 g, 8.77 mmol) in toluene was heated 4 h at 60° C. to form a white solid. After cooling to room temperature, the solids were collected by filtration and rinsed with hexanes (2×30 mL). The solids were dissolved in DCM (5 mL) and charged dropwise with TFA (5 mL). After 30 min, the reaction mixture was concentrated under reduced pressure to yield 3-((2-aminoethyl)-dimethylammonio)propane-1-sulfonate as a white solid (2.15 g). This quartarnary amine (82 mg, 0.266 mmol) was added 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 (100 mg, 0.1776 mmol) in DMF (1 mL) followed by DIPEA (137 mg, 1.06 mmol) and HATU (74.2 mg, 0.195 mmol). After 20 min, the reaction was determined to be complete by LC-MS. The product mixture was concentrated and purified by HPLC (MeCN/H2O, 10-99%) to yield the title compound as a white solid (85 mg). 1H NMR (400 MHz, MeOD) δ 8.96 (t, J=5.3 Hz, 1H), 7.88 (s, 1H), 7.79 (s, 1H), 7.60 (dd, J=10.0, 1.6 Hz, 1H), 7.28-7.18 (m, 1H), 6.98 (d, J=8.6 Hz, 1H), 6.95 (d, J=8.6 Hz, 1H) 6.57-6.52 (m, 2H), 6.51-6.45 (m, 2H), 4.18 (s, 2H), 3.89 (t, J=5.5 Hz, 2H), 3.75 (s, 3H), 3.68-3.56 (m, 4H), 3.23 (s, 6H), 2.87 (t, J=6.7 Hz, 2H), 2.25 (dt, J=14.2, 7.1 Hz, 2H), 1.60 (s, 6H). LC-MS: 655.3 [M]+.

후처리

  1. concentrationThe product mixture was concentrated
  2. custompurified by HPLC (MeCN/H2O, 10-99%)

출처 및 근거

ORD 기록
ord-98a04988be164e5aa8d78ebde04ca9b9
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846739B2

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