Hydrochloric Acid → (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide

HRID 19410ノート

反応式

HRID 19410 の反応式
CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[C@@H:15]([N:21]3[CH2:25][C:24]([O:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[Cl:33])=[CH:23][C:22]3=[O:34])[CH2:16][CH:17]([CH3:20])[CH2:18][CH3:19])=[N:9]2)[CH2:4][O:3]1.Cl>O1CCCC1>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[C@@H:15]([N:21]2[CH2:25][C:24]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:33])=[CH:23][C:22]2=[O:34])[CH2:16][CH:17]([CH3:20])[CH2:18][CH3:19])=[N:9]1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 66899949(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

生成物 1

HCID 66899111(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide収率 86%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (360 mg, 0.7 mmol) in tetrahydrofuran (15 mL) was treated with 2N aqueous hydrochloric acid (7.5 mL) and stirred at room temperature for 2.5 h. At this time the mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue was purified by ISCO flash chromatography (RediSep silica column 12 g, 30% to 80% (10% methanol/dichloromethane)hexanes) which afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (285 mg, 86%) as a white fluffy solid: HR-ES-MS (m/z) calculated for C23H29ClN4O5 [M+H]+ 477.1899, observed 477.1897. 1H NMR showed mixture of diastereomers (400 MHz, DMSO-d6) δ ppm 0.77-0.96 (m, 6H), 1.04-1.93 (m, 5H), 3.23-3.33 (m, 2H), 3.77 (br. s., 1H), 3.82-3.91 (m, 1H), 4.04-4.14 (m, 1H), 4.11-4.29 (m, 1H), 4.58, 4.63 (2×d, J=18.7 Hz, 1H), 4.71 (br. s., 1H), 4.79, 4.81 (2×s, 1H), 4.86-4.97 (m, 2H), 6.42 (br. s., 1H), 7.37 (t, J=7.7 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 7.49-7.56 (m, 2H), 7.65 (d, J=7.9 Hz, 1H), 10.77, 10.79 (2×s, 1H)

後処理

  1. customAt this time the mixture was partitioned between ethyl acetate and water
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated in vacuo
  8. customthe residue was purified by ISCO flash chromatography (RediSep silica column 12 g, 30% to 80% (10% methanol/dichloromethane)hexanes) which

出典と根拠

ORDレコード
ord-f003766450d34b18912f53af32e906ea
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

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