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Diisopropylethylamine → tert-Butyl 1-(3-{[4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoyl]amino}benzyl)cyclopropanecarboxylate

HRID 877257
ノート
印刷プレビュー

反応式

HRID 877257 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1.[F:19][C:20]([F:46])([F:45])[CH:21]([CH3:44])[CH:22]([C:26]1[CH:31]=[CH:30][C:29]([CH2:32][N:33]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][C:39]=3[F:42])[C:34]2=[O:43])=[CH:28][CH:27]=1)[C:23](O)=[O:24].O.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[F:46][C:20]([F:19])([F:45])[CH:21]([CH3:44])[CH:22]([C:26]1[CH:27]=[CH:28][C:29]([CH2:32][N:33]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][C:39]=3[F:42])[C:34]2=[O:43])=[CH:30][CH:31]=1)[C:23]([NH:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:13])[CH3:14])=[O:10])[CH2:8][CH2:7]1)=[O:24]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136514tert-Butyl 1-(3-aminobenzyl)cyclopropanecarboxylateHCID 581367454,4,4-Trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid

生成物

1
HCID 58136669tert-Butyl 1-(3-{[4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoyl]amino}benzyl)cyclopropanecarboxylate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

110.8 mg (0.41 mmol) of tert-butyl 1-(3-aminobenzyl)cyclopropanecarboxylate were added to a solution of 129.0 mg (0.33 mmol) of 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid and 52.9 mg (0.39 mmol) of 1-hydroxy-1H-benzotriazole hydrate in 1 ml of DMF. At 0° C., 142 μl (0.82 mmol) of DIEA and then, a little at a time, 136.5 mg (0.36 mmol) of HATU were added to the resulting mixture. The reaction mixture was then slowly warmed to RT and stirred at RT for 2.5 h. The mixture was added to water and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient). This gave 97.4 mg (47.6% of theory) of the title compound.

後処理

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe combined organic phases were dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient)

出典と根拠

ORDレコード
ord-4c38c5f9bc584aaf9d83229306163b46
出典データセット
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08987256B2

反応ノート

読み込み中…

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