Diisopropylethylamine → 3-Bromo-5-{[butyl(methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide Dihydrochloride

HRID 348933

反応式

HRID 348933 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12][N:13]([CH2:15][CH2:16][CH2:17][CH3:18])[CH3:14])[CH:11]=1)[C:5]([O:7]C)=O.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[ClH:52].Cl.[NH2:54][C@@H:55]([CH2:69][C:70]1[CH:75]=[C:74]([F:76])[CH:73]=[C:72]([F:77])[CH:71]=1)[C@H:56]([OH:68])[CH2:57][NH:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([CH2:66][CH3:67])[CH:61]=1>O1CCCC1.CO.O.O.[OH-].[Li+].C(Cl)Cl>[ClH:52].[ClH:52].[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12][N:13]([CH2:15][CH2:16][CH2:17][CH3:18])[CH3:14])[CH:11]=1)[C:5]([NH:54][C@@H:55]([CH2:69][C:70]1[CH:71]=[C:72]([F:77])[CH:73]=[C:74]([F:76])[CH:75]=1)[C@H:56]([OH:68])[CH2:57][NH:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([CH2:66][CH3:67])[CH:61]=1)=[O:7]

参加物

8

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 21086161Methyl 3-bromo-5-{[butyl(methyl)amino]methyl}benzoateHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

生成物 1

HCID 686088113-Bromo-5-{[butyl(methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide Dihydrochloride

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 168937Lithium hydroxide, monohydrate溶媒HCID 21892291Methanol tetrahydrofuran water溶媒

実験手順

Methyl 3-bromo-5-{[butyl(methyl)amino]methyl}benzoate prepared by the method in EXAMPLE SP-190, Step 1 (170 mg, 0.54) is dissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL), and lithium hydroxide monohydrate is added (45 mg, 1.1 mmol), and the reaction stirred 16 h. The solution is concentrated under reduced pressure. The residue is redissolved in DMF (5 mL), and diisopropylethylamine (375 μL, 2.16 mmol), HATU (256 mg, 0.68 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method in EXAMPLE SP-272 (265 mg, 0.65 mmol) are added. The reaction stirred at room temperature 1 h. The reaction mixture is diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/methylene chloride) provides the title compound as the free base. The residue is dissolved in diethyl ether (3 mL) and 1N hydrochloric acid in diethyl ether (1 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 616.2 [M+H]+.

後処理

  1. additionis added (45 mg, 1.1 mmol)
  2. concentrationThe solution is concentrated under reduced pressure
  3. dissolutionThe residue is redissolved in DMF (5 mL)
  4. additionare added
  5. stirringThe reaction stirred at room temperature 1 h
  6. washwashed with water, and saturated sodium bicarbonate
  7. dry with materialdried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (silica, 8% methanol/methylene chloride)

出典と根拠

ORDレコード
ord-11ac6f0e227c42f882ed4027d76c3999
出典データセット
uspto-grants-2007_02
特許番号
US07176242B2

関連ノート

読み込み中…