Sodium Carbonate → (2-Chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)methanol

HRID 40283

Reaction equation

HRID 40283 reaction equation
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:27]=[C:28](CO)[CH:29]=[CH:30][C:31]=1B1OC(C)(C)C(C)(C)O1.[C:43](=[O:46])([O-])[O-].[Na+].[Na+]>COCCOC.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:27]=[C:28]([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:30][C:31]=1[CH2:43][OH:46]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 250669924-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinolineHCID 53217321(3-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol

Product 1

HCID 57691052(2-Chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)methanol

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (200 mg, 585 μmol), (3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol (173 mg, 644 μmol), dichloro[1,1′bis(diphenylphoshino)ferrocene]palladium(ii)dichloromethane adduct (21 mg, 29 μmol), and sodium carbonate (2M; 1170 μl, 2341 μmol) in DME (2 mL) was sparged with argon for 10 min then heated to 85° C. for 6 h. Reaction then partitioned between 9:1 CHCl3/IPA (25 mL) and 5% NaHCO3 (10 mL) and aqueous further extracted with 9:1 CHCl3/IPA (2×10 mL). Combined organics dried with MgSO4 then concentrated onto dry silica under reduced pressure. Product purified on 40 g silica eluting with 0>12% of 2M NH3 in MeOH/DCM and isolated as an off white powder. MS (ESI pos. ion) m/z: 448 (MH+). Calc'd exact mass for C23H18ClN5O3: 447.

Workup

  1. customwas sparged with argon for 10 min
  2. customReaction
  3. customthen partitioned between 9:1 CHCl3/IPA (25 mL) and 5% NaHCO3 (10 mL)
  4. extractionaqueous further extracted with 9:1 CHCl3/IPA (2×10 mL)
  5. dry with materialCombined organics dried with MgSO4
  6. concentrationthen concentrated onto dry silica under reduced pressure
  7. customProduct purified on 40 g silica eluting with 0>12% of 2M NH3 in MeOH/DCM
  8. customisolated as an off white powder

Sources & evidence

ORD record
ord-f27259811247442ba40233678503eed8
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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