Diisopropylethylamine → N1-Butyl-N3-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N1-methyl-5-(1,3-thiazol-2-yl)isophthalamide

HRID 14307ノート

反応式

HRID 14307 の反応式
[CH2:1]([N:5]([CH3:22])[C:6]([C:8]1[CH:9]=[C:10]([CH:14]=[C:15]([C:17]2[S:18][CH:19]=[CH:20][N:21]=2)[CH:16]=1)[C:11]([OH:13])=O)=[O:7])[CH2:2][CH2:3][CH3:4].[CH:23](N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:58][C@@H:59]([CH2:75][C:76]1[CH:81]=[C:80]([F:82])[CH:79]=[C:78]([F:83])[CH:77]=1)[C@H:60]([OH:74])[CH2:61][NH:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[C:66]([C:70](F)(F)F)[CH:65]=1>CN(C=O)C.C(Cl)(Cl)Cl>[CH2:1]([N:5]([CH3:22])[C:6](=[O:7])[C:8]1[CH:16]=[C:15]([C:17]2[S:18][CH:19]=[CH:20][N:21]=2)[CH:14]=[C:10]([C:11]([NH:58][C@@H:59]([CH2:75][C:76]2[CH:81]=[C:80]([F:82])[CH:79]=[C:78]([F:83])[CH:77]=2)[C@H:60]([OH:74])[CH2:61][NH:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:23])[CH:65]=2)=[O:13])[CH:9]=1)[CH2:2][CH2:3][CH3:4]

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 210857333-{[Butyl(methyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoic acidHCID 57487373(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol dihydrochloride

生成物 1

HCID 10282843N1-Butyl-N3-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N1-methyl-5-(1,3-thiazol-2-yl)isophthalamide

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6228Dimethylformamide溶媒

実験手順

3-{[Butyl(methyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoic acid (125 mg, 0.39 mmol) is dissolved in DMF (3 mL), and diisopropylethylamine (271 μL, 1.6 mmol), HATU (178 mg, 0.47 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol dihydrochloride (176 mg, 0.43 mmol) are added. The reaction stirred at room temperature 4 h. The reaction mixture is diluted with chloroform, washed with water, saturated sodium bicarbonate, saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/methylene chloride) provides the title compound as the free base. The residue is dissolved in diethyl ether (3 mL) and 1N hydrochloric acid in diethyl ether (2 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 635.3 [M+H]+.

後処理

  1. washwashed with water, saturated sodium bicarbonate, saturated sodium chloride
  2. dry with materialdried (sodium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 8% methanol/methylene chloride)

出典と根拠

ORDレコード
ord-b9c2a0c919964a5ba723c66a3dbc2f60
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

反応ノート

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