Hydrochloric Acid → (2S)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-((S)-1-hydroxypropan-2-yloxy)propanamide

HRID 1098039노트

반응식

HRID 1098039 반응식
Cl.[Si]([O:9][CH2:10][C@@H:11]([O:13][CH2:14][C@H:15]([O:26][C:27]1[N:32]=[CH:31][N:30]=[C:29]2[N:33]([C:36]3[C:41]([Cl:42])=[CH:40][CH:39]=[CH:38][N:37]=3)[N:34]=[CH:35][C:28]=12)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][N:20]=1)=[O:17])[CH3:12])(C(C)(C)C)(C)C>C1COCC1.O>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:16](=[O:17])[C@@H:15]([O:26][C:27]2[N:32]=[CH:31][N:30]=[C:29]3[N:33]([C:36]4[C:41]([Cl:42])=[CH:40][CH:39]=[CH:38][N:37]=4)[N:34]=[CH:35][C:28]=23)[CH2:14][O:13][C@@H:11]([CH3:12])[CH2:10][OH:9])=[N:20][CH:21]=1

참가 물질

5

반응물 2

HCID 313Hydrochloric AcidHCID 57504541(2S)-3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-yloxy)propanamide

생성물 1

HCID 57504421(2S)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-((S)-1-hydroxypropan-2-yloxy)propanamide수율 71.5%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

HCl (4M in Dioxane) (0.606 mL, 2.42 mmol) was added to (2S)-3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AO4) (300 mg, 0.48 mmol) in THF (5 mL) and water (0.5 mL) at room temperature. The resulting solution was stirred at room temperature for 10 minutes. The reaction mixture was evaporated and the residue partitioned between EtOAc (25 mL) and sat NaHCO3 (10 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by preparative chiral-HPLC on a Merck 50 mm 20 μm Chiralpak AS column, eluting isocratically with 30% EtOH in isohexane (modified with Et3N) as eluent. The fractions containing the desired compound were evaporated to dryness to afford the product (173 mg, 70.7%). 1H NMR (400 MHz, CDCl3) δ 1.17 (d, 3H), 2.64 (s, 1H), 3.51-3.67 (m, 2H), 3.69-3.79 (m, 1H), 4.11-4.28 (m, 2H), 6.05 (t, 1H), 7.45-7.50 (m, 1H), 7.66-7.71 (m, 1H), 7.99-8.04 (m, 1H), 8.18-8.25 (m, 2H), 8.47 (s, 1H), 8.60-8.65 (m, 2H), 9.10 (s, 1H) m/z (ESI+) (M+H)+=504.40; HPLC tR=1.96 min

후처리

  1. customThe reaction mixture was evaporated
  2. customthe residue partitioned between EtOAc (25 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated
  5. customThe crude product was purified by preparative chiral-HPLC on a Merck 50 mm 20 μm Chiralpak AS column
  6. washeluting isocratically with 30% EtOH in isohexane (modified with Et3N) as eluent
  7. additionThe fractions containing the desired compound
  8. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-503faddf7b72454f803c13dfa9b52d76
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143263B2

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