Dichloromethane → (S)-N-(4-((R)-3-aminopyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide hydrochloride

HRID 875904노트

반응식

HRID 875904 반응식
[Br:1][C:2]1[C:3]([N:17]2[CH2:21][CH2:20][C@@H:19]([NH:22]C(=O)OC(C)(C)C)[CH2:18]2)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[C@@H:13]([OH:15])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:38]>>[ClH:38].[NH2:22][C@@H:19]1[CH2:20][CH2:21][N:17]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:16])[C@@H:13]([OH:15])[CH3:14])[C:4]=23)[CH2:18]1

참가 물질

4

반응물 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 60205673tert-butyl (R)-1-(5-bromo-3-((S)-2-hydroxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate

생성물 1

HCID 60205674(S)-N-(4-((R)-3-aminopyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide hydrochloride수율 58%

실험 절차

tert-Butyl (R)-1-(5-bromo-3-((S)-2-hydroxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate (0.040 g, 0.085 mmol) was placed in DCM (3 mL) at room temperature. TFA (1 mL) was then added, and the reaction was stirred at room temperature for 1 hour and concentrated to dryness. The resulting residue was then purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 0-50% CH3CN/water). The resulting product was next dissolved in minimal DCM (with MeOH to aid solubility) and added to a stirring solution of 1M HCl in ether. The resulting solid was filtered, washed with ether and dried to give (S)—N-(4-((R)-3-aminopyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide hydrochloride (0.022 g, 58% yield). 1H NMR (400 MHz, D2O) δ 8.16 (s, 1H), 7.50 (s, 1H), 4.32-4.30 (q, 1H), 4.03-4.00 (m, 1H), 3.89-3.84 (m, 1H), 3.66-3.63 (m, 1H), 3.59-3.55 (m, 1H), 3.48-3.46 (m, 1H), 2.42-2.39 (m, 1H), 2.07-2.04 (m, 1H), 1.34-1.32 (d, 3H); LCMS (APCI+) m/z 368, 370 (M+H)+.

후처리

  1. concentrationconcentrated to dryness
  2. customThe resulting residue was then purified by reverse phase chromatography (Biotage SP4
  3. dissolutionThe resulting product was next dissolved in minimal DCM (with MeOH to aid solubility)
  4. additionadded to a stirring solution of 1M HCl in ether
  5. filtrationThe resulting solid was filtered
  6. washwashed with ether
  7. customdried

출처 및 근거

ORD 기록
ord-8f84cbcaeffa4dd682b6bd2339d0e792
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08981085B2

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