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Diisopropylethylamine → Isobutyl 3-(5-((1R,2S)-1-(4H-benzo[d][1,3]dioxin-7-yl)-2-(2,2-difluoropropanamido)propoxy)-1H-indazol-1-yl)benzoate

HRID 1406588
ノート
印刷プレビュー

反応式

HRID 1406588 の反応式
[NH2:1][C@@H:2]([CH3:37])[C@@H:3]([C:27]1[CH:28]=[CH:29][C:30]2[CH2:35][O:34][CH2:33][O:32][C:31]=2[CH:36]=1)[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([O:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[O:18])[N:9]=[CH:8]2.[F:38][C:39]([F:44])([CH3:43])[C:40](O)=[O:41].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>ClCCl.O>[O:32]1[C:31]2[CH:36]=[C:27]([C@@H:3]([O:4][C:5]3[CH:6]=[C:7]4[C:11](=[CH:12][CH:13]=3)[N:10]([C:14]3[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=3)[C:17]([O:19][CH2:20][CH:21]([CH3:22])[CH3:23])=[O:18])[N:9]=[CH:8]4)[C@@H:2]([NH:1][C:40](=[O:41])[C:39]([F:44])([F:38])[CH3:43])[CH3:37])[CH:28]=[CH:29][C:30]=2[CH2:35][O:34][CH2:33]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27828252,2-Difluoropropionic acidHCID 59272925HCID 59272925、化合物

生成物 1

HCID 59272926Isobutyl 3-(5-((1R,2S)-1-(4H-benzo[d][1,3]dioxin-7-yl)-2-(2,2-difluoropropanamido)propoxy)-1H-indazol-1-yl)benzoate
収率 80.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒2 回

実験手順

A mixture of isobutyl 3-(5-((1R,2S)-2-amino-1-(4H-benzo[d][1,3]dioxin-7-yl)propoxy)-1H-indazol-1-yl)benzoate (420 mg, 0.84 mmol) (I5b), 2,2-difluoropropanoic acid (213 mg, 1.94 mmol) and HBTU (420 mg, 1.11 mmol) were suspended in dichloromethane (10 mL). N-ethyl-N-isopropylpropan-2-amine (0.85 mL, 5.13 mmol) was added and the mixture was stirred at room temperature overnight. Water (ca 10 mL) was added to the solution. After stirring for some minutes the mixture was added to a phase separator. The water phase was stirred with dichloromethane (5 mL) and added to the phase separator. The combined organic phases were concentrated to a brown oil. Purification by flash chromatography on silica (dichloromethane/ethyl acetate 10/1) gave the title compound as a white foam (400 mg, 80%).

後処理

  1. stirringAfter stirring for some minutes the mixture
  2. additionwas added to a phase separator
  3. additionadded to the phase separator
  4. concentrationThe combined organic phases were concentrated to a brown oil
  5. customPurification by flash chromatography on silica (dichloromethane/ethyl acetate 10/1)

出典と根拠

ORDレコード
ord-9dab6b4d9c87436a9e03e4be58e09b23
出典データセット
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08916600B2

反応ノート

読み込み中…

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