Diisopropylethylamine → N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(1H-imidazol-2-yl)-N3,N3-dipropylisophthalamide

HRID 14064

反応式

HRID 14064 の反応式
[CH2:1]([N:4]([CH2:21][CH2:22][CH3:23])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[NH:17][CH:18]=[CH:19][N:20]=2)[CH:15]=1)[C:10]([OH:12])=O)=[O:6])[CH2:2][CH3:3].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][C@@H:58]([CH2:72][C:73]1[CH:78]=[C:77]([F:79])[CH:76]=[C:75]([F:80])[CH:74]=1)[C@H:59]([OH:71])[CH2:60][NH:61][CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[C:65]([CH2:69][CH3:70])[CH:64]=1>C(Cl)Cl>[F:79][C:77]1[CH:78]=[C:73]([CH:74]=[C:75]([F:80])[CH:76]=1)[CH2:72][C@H:58]([NH:57][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([C:16]2[NH:17][CH:18]=[CH:19][N:20]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:21][CH2:22][CH3:23])=[O:6])[CH:8]=1)[C@H:59]([OH:71])[CH2:60][NH:61][CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[C:65]([CH2:69][CH3:70])[CH:64]=1

参加物

6

反応物 4

HCID 81531Diisopropylethylamine2 回HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210857853-[(Dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoic AcidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

生成物 1

HCID 58802851N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(1H-imidazol-2-yl)-N3,N3-dipropylisophthalamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a stirred solution of 3-[(dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoic acid (250 mg, 0.79 mmol), diisopropylethylamine (103 mg, 0.8 mmol), and HBTU (330 mg, 0.87 mmol) in methylene chloride (5 mL) is added a mixture of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (322 mg, 0.79 mmol) and diisopropylethylamine (206 mg, 1.6 mmol) in methylene chloride (5 mL). The reaction mixture is stirred at room temperature for 4 h and concentrated under reduced pressure. The residue is diluted with ethyl acetate (20 mL), washed with saturated sodium bicarbonate, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 5:95 methanol/methylene chloride) provides the title compound in pure form. APCI MS m/z 632.3 [M+H]+.

後処理

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue is diluted with ethyl acetate (20 mL)
  3. washwashed with saturated sodium bicarbonate, and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (silica gel, 5:95 methanol/methylene chloride)

出典と根拠

ORDレコード
ord-a46e1ee47536492eb043e03e19909d12
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

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