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 1454202ノート

反応式

HRID 1454202 の反応式
[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]

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 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

生成物 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 ester収率 99.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-2c86f4892ee94565b8d8bfaf24a785fb
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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