Diisopropylethylamine → [(2R,3S)-3-[3-acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoylamino]-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-methoxy-benzyl)-carbamic acid tert-butyl ester

HRID 1454202노트

반응식

HRID 1454202 반응식
[C:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][S:14]2(=[O:20])=[O:19])[CH:12]=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].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.[CH3:54][O:55][C:56]1[CH:57]=[C:58]([CH:82]=[CH:83][CH:84]=1)[CH2:59][N:60]([CH2:68][C@@H:69]([OH:81])[C@@H:70]([NH2:80])[CH2:71][C:72]1[CH:77]=[C:76]([F:78])[CH:75]=[C:74]([F:79])[CH:73]=1)[C:61](=[O:67])[O:62][C:63]([CH3:66])([CH3:65])[CH3:64]>CN(C=O)C.C(OCC)(=O)C>[C:63]([O:62][C:61](=[O:67])[N:60]([CH2:68][C@@H:69]([OH:81])[C@@H:70]([NH:80][C:7](=[O:9])[C:6]1[CH:10]=[C:11]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][S:14]2(=[O:20])=[O:19])[CH:12]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1)[CH2:71][C:72]1[CH:77]=[C:76]([F:78])[CH:75]=[C:74]([F:79])[CH:73]=1)[CH2:59][C:58]1[CH:82]=[CH:83][CH:84]=[C:56]([O:55][CH3:54])[CH:57]=1)([CH3:66])([CH3:64])[CH3:65]

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 575293073-Acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoic acidHCID 68827600tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate

생성물 1

HCID 57529282[(2R,3S)-3-[3-acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoylamino]-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-methoxy-benzyl)-carbamic acid tert-butyl ester수율 99.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 3-acetyl-5-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-benzoic acid (68.1 mg, 0.23 mmol), HATU (104.6 mg, 0.275 mmol) and Hunig's base (118.5 mg, 0.16 mL, 0.917 mmol) in DMF (1.1 mL) was stirred for 10 min and then tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate (100 mg, 0.23 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate, washed with H2O 3 times and concentrated under vacuum to give the title compound (164 mg): 1H NMR (CD3OD, 500 MHz) δ ppm 1.48 (9H, s), 1.93-2.00 (2H, m), 2.32-2.38 (2H, m), 2.64 (3H, s), 2.88 (1H, dd, J=10, 15 Hz), 3.08-3.15 (1H, m), 3.20-3.23 (1H, m), 3.27-3.39 (2H, m), 3.38 (1H, m), 3.74-3.82 (6H, m), 3.96-4.00 (1H, m), 4.20-4.29 (2H, m), 6.76 (1H, m), 6.91-6.92 (3H, m), 7.05-7.08 (2H, m), 7.35 (1H, m), 8.04 (1H, m), 8.07 (1H, m), 8.11 (1H, m). HPLC retention time: 2.112 min (method A). MS (ESI) (M+Na)+ 738.28.

후처리

  1. stirringThe reaction mixture was stirred at room temperature for 2 h
  2. washwashed with H2O 3 times
  3. concentrationconcentrated under vacuum

출처 및 근거

ORD 기록
ord-2c86f4892ee94565b8d8bfaf24a785fb
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07476764B2

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