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

HRID 875908노트

반응식

HRID 875908 반응식
[Br:1][C:2]1[C:3]([N:18]2[CH2:22][CH2:21][C@@H:20]([NH:23]C(=O)OC(C)(C)C)[CH2:19]2)=[C:4]2[C:10]([NH:11][C:12](=[O:17])[C@@H:13]([O:15][CH3:16])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:39]>>[ClH:39].[NH2:23][C@@H:20]1[CH2:21][CH2:22][N:18]([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:17])[C@@H:13]([O:15][CH3:16])[CH3:14])[C:4]=23)[CH2:19]1

참가 물질

4

반응물 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 60205678tert-butyl (R)-1-(5-bromo-3-((S)-2-methoxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate

생성물 1

HCID 60205679(S)-N-(4-((R)-3-aminopyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide hydrochloride수율 90%

실험 절차

tert-Butyl (R)-1-(5-bromo-3-((S)-2-methoxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate (0.41 g, 0.85 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-methoxypropanamide hydrochloride (0.35 g, 90% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.17 (s, 1H), 7.39 (s, 1H), 4.03-3.96 (m, 3H), 3.95-3.79 (m, 1H), 3.73-3.69 (m, 1H), 3.60-3.53 (m, 1H), 3.36 (s, 3H), 2.40-2.35 (m, 1H), 2.07-2.02 (m, 1H), 1.31-1.29 (d, 3H). LCMS (APCI+) m/z 382, 384 (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-c5d3a4fc957d4f12979631c01c58b4f6
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08981085B2

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