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

HRID 423032

반응식

HRID 423032 반응식
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

참가 물질

6

반응물 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 acid2회

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3e892a1c89964a72a959f53ebe6037bb
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101623B2

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