Diisopropylethylamine → HCID 178489994、化合物

HRID 1627264ノート

反応式

HRID 1627264 の反応式
[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]

参加物

6

反応物 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、化合物

生成物 1

HCID 178489994HCID 178489994、化合物収率 91%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-dc242b52150f412a98b7e783207b6272
出典データセット
uspto-grants-2014_07
特許番号
US08785488B2

反応ノート

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