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

HRID 1098038
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HRID 1098038 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]([F:25])=[CH:21][N:20]=1)=[O:17])[CH3:12])(C(C)(C)C)(C)C>C1COCC1>[Cl:42][C:41]1[C:36]([N:33]2[C:29]3=[N:30][CH:31]=[N:32][C:27]([O:26][C@@H:15]([CH2:14][O:13][C@@H:11]([CH3:12])[CH2:10][OH:9])[C:16]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][N:20]=4)=[O:17])=[C:28]3[CH:35]=[N:34]2)=[N:37][CH:38]=[CH:39][CH:40]=1
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참가 물질

4

반응물 2

HCID 313Hydrochloric AcidHCID 57504540(2S)-3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide

생성물 1

HCID 57504420(2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)-3-((S)-1-hydroxypropan-2-yloxy)propanamide수율 77%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran
용매

실험 절차

HCl (4M in Dioxane) (0.530 mL, 2.12 mmol) was added to (2S)-3-((S)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide (Intermediate AO3) (638 mg, 1.06 mmol) in THF (5 mL) at room temperature. The resulting solution was stirred for 20 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 to afford the product (397 mg, 77%). 1H NMR (400 MHz, CDCl3) δ1.16 (d, 3H), 2.73 (s, 1H), 3.51-3.68 (m, 2H), 3.69-3.78 (m, 1H), 4.12-4.28 (m, 2H), 6.06 (t, 1H), 7.42-7.50 (m, 2H), 7.99-8.03 (m, 1H), 8.13 (d, 1H), 8.21-8.26 (m, 1H), 8.47 (s, 1H), 8.60-8.65 (m, 2H), 9.09 (s, 1H); m/z (ESI+) (M+H)+=488.42; HPLC tR=1.75 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

출처 및 근거

ORD 기록
ord-5fff1b2295244f28ac0e20c1c8e9e22e
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08143263B2

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