Diisopropylethylamine → tert-butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(methylsulfonyl)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate

HRID 1454198ノート

反応式

HRID 1454198 の反応式
C[C:2]1[C:10]([C:11](=[O:13])[CH3:12])=[CH:9][C:8]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:7][C:3]=1[C:4]([OH:6])=O.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.[CH3:51][O:52][C:53]1[CH:54]=[C:55]([CH:79]=[CH:80][CH:81]=1)[CH2:56][N:57]([CH2:65][C@@H:66]([OH:78])[C@@H:67]([NH2:77])[CH2:68][C:69]1[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[CH:70]=1)[C:58](=[O:64])[O:59][C:60]([CH3:63])([CH3:62])[CH3:61]>CN(C=O)C.C(OCC)(=O)C>[CH3:51][O:52][C:53]1[CH:54]=[C:55]([CH:79]=[CH:80][CH:81]=1)[CH2:56][N:57]([CH2:65][C@@H:66]([OH:78])[C@@H:67]([NH:77][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([S:14]([CH3:17])(=[O:15])=[O:16])[CH:9]=[C:10]([C:11](=[O:13])[CH3:12])[CH:2]=1)[CH2:68][C:69]1[CH:70]=[C:71]([F:76])[CH:72]=[C:73]([F:75])[CH:74]=1)[C:58](=[O:64])[O:59][C:60]([CH3:63])([CH3:61])[CH3:62]

参加物

7

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 68827600tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamateHCID 68830431Methyl 3-acetyl-5-(methylsulfonyl)benzoic acid

生成物 1

HCID 57529302tert-butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(methylsulfonyl)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate収率 49.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of methyl 3-acetyl-5-(methylsulfonyl)benzoic acid (52 mg, 0.215 mmol), HATU (98 mg, 0.258 mmol) and Hunig's base (111.1 mg, 0.15 mL, 0.86 mmol) in DMF (1.0 mL) was stirred for 10 min and then tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate (94 mg, 0.215 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with H2O 3 times and concentrated under vacuum. The crude mixture was purified by reverse phase prep HPLC to give the title compound (70 mg): 1H NMR (CD3OD, 500 MHz) δ ppm 1.48 (9H, s), 2.70 (3H, s), 2.87-2.90 (1H, m), 3.11-3.15 (2H, m), 3.20 (3H, s), 3.37 (1H, m), 3.76 (3H, s), 3.79-3.80 (1H, m), 3.99 (1H, m), 4.33-4.39 (1H, m), 4.43-4.47 (1H, m), 6.73 (1H, m), 6.80-6.83 (3H, m), 6.91 (2H, m), 7.21-7.25 (1H, m), 8.45 (1H, m), 8.54 (1H, m), 8.61 (1H, m). HPLC retention time: 2.022 min (method B). MS (ESI) (M+H)+ 661.14.

後処理

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. washwashed with H2O 3 times
  3. concentrationconcentrated under vacuum
  4. customThe crude mixture was purified by reverse phase prep HPLC

出典と根拠

ORDレコード
ord-b0bdea22bba44a7787550390eebcddc4
出典データセット
uspto-grants-2009_01
特許番号
US07476764B2

反応ノート

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