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 1098039ノート

反応式

HRID 1098039 の反応式
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

参加物

5

反応物 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

生成物 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)propanamide収率 71.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-503faddf7b72454f803c13dfa9b52d76
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

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