Diisopropylethylamine → (S)-tert-butyl (4-(1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methylcarbamate

HRID 423032

反応式

HRID 423032 の反応式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([NH:32][CH2:33][C:34]1([C:49]([OH:51])=O)[CH2:39][CH2:38][N:37]([C:40]2[C:41]3[CH:48]=[CH:47][NH:46][C:42]=3[N:43]=[CH:44][N:45]=2)[CH2:36][CH2:35]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].[Cl:52][C:53]1[CH:58]=[CH:57][C:56]([C@@H:59]([NH2:61])[CH3:60])=[CH:55][CH:54]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[Cl:52][C:53]1[CH:58]=[CH:57][C:56]([C@@H:59]([NH:61][C:49]([C:34]2([CH2:33][NH:32][C:30](=[O:31])[O:29][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:35][CH2:36][N:37]([C:40]3[C:41]4[CH:48]=[CH:47][NH:46][C:42]=4[N:43]=[CH:44][N:45]=3)[CH2:38][CH2:39]2)=[O:51])[CH3:60])=[CH:55][CH:54]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 1550852(S)-(-)-1-(4-chlorophenyl)ethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 446042214-((tert-butoxycarbonylamino)methyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid2 回

生成物 1

HCID 57750334(S)-tert-butyl (4-(1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methylcarbamate収率 83.5%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
60 °C

実験手順

HATU (0.251 g, 0.66 mmol) was added in one portion to 4-((tert-butoxycarbonylamino)methyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 12) (0.225 g, 0.6 mmol), (S)-1-(4-chlorophenyl)ethanamine (0.093 g, 0.60 mmol) and DIPEA (0.314 mL, 1.80 mmol) in DMA (10 mL) at 25° C. under nitrogen. The resulting solution was stirred at 60° C. for 4 hours. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using methanol. Residual HATU was removed by passing the methanol solution through a silica-supported carbonate column. The crude product thus obtained was evaporated to dryness to afford (S)-tert-butyl (4-(1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methylcarbamate (0.257 g, 83%) as a colourless gum. This material was used directly in the next step without further purification.

後処理

  1. customThe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customResidual HATU was removed
  4. customThe crude product thus obtained
  5. customwas evaporated to dryness

出典と根拠

ORDレコード
ord-3e892a1c89964a72a959f53ebe6037bb
出典データセット
uspto-grants-2012_01
特許番号
US08101623B2

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