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Lithium Hydroxide → (R)-tert-butyl 1-(5-bromo-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 2203946
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HRID 2203946 반응식
[C:1](Cl)(=[O:4])[CH2:2][CH3:3].[NH2:6][C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Br:30])[C:14]=2[N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:17]2)[NH:9][CH:8]=1.[Li+].[OH-]>CN1C(=O)CCC1.C(Cl)Cl.O.N1C=CC=CC=1>[Br:30][C:13]1[C:14]([N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:17]2)=[C:15]2[C:7]([NH:6][C:1](=[O:4])[CH2:2][CH3:3])=[CH:8][NH:9][C:10]2=[N:11][CH:12]=1
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참가 물질

8

반응물 3

HCID 3939Lithium HydroxideHCID 62324Propionyl chlorideHCID 67045407(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

생성물 1

HCID 67045151(R)-tert-butyl 1-(5-bromo-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate수율 52.8%

시약·촉매·용매 4

HCID 962Water
용매
HCID 1049Pyridine용매
HCID 6344Dichloromethane용매2회
HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

DCM (2 mL), pyridine (0.5 mL) and propionyl chloride (0.180 g, 1.95 mmol) were added to (R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.200 g, 0.487 mmol; Example 98, Step A) in NMP (3 mL). The reaction was then stirred for 1 hour at room temperature. 3M aqueous LiOH (3 mL) was then added, and the reaction was stirred for 10 minutes. Water (10 mL) and DCM (10 mL) were then added, and the organic fraction was dried, filtered and concentrated to give the crude product. Purification by reverse phase HPLC (5-95% ACN in water) gave the product (R)-tert-butyl 1-(5-bromo-3-propionamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.120 g, 52.8% yield).

후처리

  1. stirringthe reaction was stirred for 10 minutes
  2. customthe organic fraction was dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product
  6. customPurification by reverse phase HPLC (5-95% ACN in water)

출처 및 근거

ORD 기록
ord-e04c9d9564b64f3caff60a93c17274ee
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09365568B2

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