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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Acetic Acid → (+/-)-2-((2-chloro-5-cyano-3-((4aR,8aR)-1-methylhexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 1430913
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HRID 1430913 반응식
[Cl:1][C:2]1[C:7]([N:8]2[CH2:17][CH2:16][C@@H:15]3[C@H:10]([O:11][CH2:12][CH2:13][NH:14]3)[CH2:9]2)=[CH:6][C:5]([C:18]#[N:19])=[CH:4][C:3]=1[NH:20][C:21]1[N:26]=[C:25]([NH:27][CH2:28][CH3:29])[C:24]2=[N:30][CH:31]=[C:32]([C:33]#[N:34])[N:23]2[N:22]=1.[CH:35](OC)(OC)OC.CC(O)=O.C=O>CO.CCOC(C)=O.C1COCC1>[Cl:1][C:2]1[C:7]([N:8]2[CH2:17][CH2:16][C@@H:15]3[C@H:10]([O:11][CH2:12][CH2:13][N:14]3[CH3:35])[CH2:9]2)=[CH:6][C:5]([C:18]#[N:19])=[CH:4][C:3]=1[NH:20][C:21]1[N:26]=[C:25]([NH:27][CH2:28][CH3:29])[C:24]2=[N:30][CH:31]=[C:32]([C:33]#[N:34])[N:23]2[N:22]=1
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참가 물질

8

반응물 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 9005Trimethyl orthoformateHCID 86708616(+/-)-2-((2-chloro-5-cyano-3-((4aR,8aR)-hexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

생성물 1

HCID 86708619(+/-)-2-((2-chloro-5-cyano-3-((4aR,8aR)-1-methylhexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile
수율 91.7%

시약·촉매·용매 3

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
25 °C

실험 절차

(+/−)-2-((2-chloro-5-cyano-3-((4aR,8aR)-hexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 371) (13 mg, 0.027 mmol) was taken up in MeOH (0.5 mL) and THF (0.5 mL) and trimethyl orthoformate (0.225 mL, 2.036 mmol), AcOH (6.22 μl, 0.109 mmol), and formaldehyde (2.492 μl, 0.027 mmol) were added. The reaction was stirred at 25° C. for 5 min, then NaCNBH4 (0.271 mL, 0.271 mmol) was added and the reaction stirred at 25° C. 1 hr. The reaction mixture was diluted with EtOAc and washed with sat'd NaHCO3, then brine. The organic layer was dried over Na2SO4, and concentrated. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 20-mM ammonium acetate; Gradient: 50-100% B over 15 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford (+/−)-2-((2-chloro-5-cyano-3-((4aR,8aR)-1-methylhexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (12.2 mg).

후처리

  1. additionNaCNBH4 (0.271 mL, 0.271 mmol) was added
  2. stirringthe reaction stirred at 25° C
  3. custom1 hr
  4. washwashed with sat'd NaHCO3
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude material was purified via preparative LC/MS with the following conditions
  8. waitGradient: 50-100% B over 15 minutes
  9. customa 5-minute hold
  10. additionFractions containing the desired product
  11. customdried via centrifugal evaporation

출처 및 근거

ORD 기록
ord-da5a82daef5e4f3b996e715fa25107ec
출처 데이터셋
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08940736B2

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