Cesium carbonate → Tert-butyl 1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)ethylcarbamate

HRID 40287

반응식

HRID 40287 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:10]=2)[N:7]=1.[Cl:25][C:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:27]=1[CH:41]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH3:42].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:25][C:26]1[CH:31]=[C:30]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH2:11][O:12][C:13]4[C:22]5[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=5)[N:16]=[CH:15][CH:14]=4)=[N:9][N:10]=3)[N:7]=2)[CH:29]=[CH:28][C:27]=1[CH:41]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH3:42]

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 250669924-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinolineHCID 57691125Tert-butyl 1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethylcarbamate

생성물 1

HCID 57691339Tert-butyl 1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)ethylcarbamate

시약·촉매·용매 3

HCID 53485975CID 53485975촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

A suspension of 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (180 mg, 527 μmol), tert-butyl 1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethylcarbamate (302 mg, 790 μmol), dichloro[1,1′bis(diphenylphoshino)ferrocene]palladium(ii)dichloromethane adduct (77.1 mg, 105 μmol), cesium carbonate (686 mg, 2107 μmol) in DMF (2 mL) and water (0.4 mL) was first sparged with argon for 5 min then heated to 100° C. with stirring. 2:20 pm After 10 min, LCMS suggests >95% conversion. Reaction then partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (5 mL). Organic then dried over MgSO4, concentrated, and purified on silica (40 g) eluting with isocratic 4% of 2M NH3 in MeOH/DCM. MS (ESI pos. ion) m/z: 561 (MH+). Calc'd exact mass for C29H29ClN6O4: 560.

후처리

  1. customwas first sparged with argon for 5 min
  2. customReaction
  3. customthen partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (5 mL)
  4. dry with materialOrganic then dried over MgSO4
  5. concentrationconcentrated
  6. custompurified on silica (40 g)
  7. washeluting with isocratic 4% of 2M NH3 in MeOH/DCM

출처 및 근거

ORD 기록
ord-c792f4ce5bf94152a32122126410b32e
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524900B2

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