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

HRID 1454198노트

반응식

HRID 1454198 반응식
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]

참가 물질

7

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b0bdea22bba44a7787550390eebcddc4
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07476764B2

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