Cesium carbonate → HCID 68810783, compound

HRID 1878788Notes

Reaction equation

HRID 1878788 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[N:7]=1.[Cl:24][C:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:26]=1[C@H:40]([NH:45][S@@:46]([C:48]([CH3:51])([CH3:50])[CH3:49])=[O:47])[C:41]([F:44])([F:43])[F:42].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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:24][C:25]1[CH:30]=[C:29]([C:2]2[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=4)[N:14]=[CH:13][CH:12]=3)[N:7]=2)[CH:28]=[CH:27][C:26]=1[C@H:40]([NH:45][S@@:46]([C:48]([CH3:51])([CH3:50])[CH3:49])=[O:47])[C:41]([F:44])([F:43])[F:42]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 57690992HCID 57690992, compoundHCID 598430126-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one

Product 1

HCID 68810783HCID 68810783, compound

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 6-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one (255 mg, 769 μmol), (R)—N—((S)-1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide (260 mg, 591 μmol), dichloro[1,1′bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct (43.3 mg, 59.1 μmol), cesium carbonate (771 mg, 2365 μmol) in 1,4-dioxane (3 mL) and water (0.75 mL) was sparged with argon for 5 minutes then heated to 90° C. with stirring for 2 hours The reaction was then partitioned between 9:1 CHCl3/IPA (25 mL) and 5% NaHCO3 (10 mL). The organic layer was then dried over MgSO4, concentrated, then purified on silica (40 g) eluting with 2 to 3% MeOH/DCM. Product was isolated as an off white solid from ACN. MS (ESI pos. ion) m/z: 609 (MH+); calc'd for C28H28ClF3N4O4S: 608. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.27 (s, 9 H) 3.87 (d, J=8.02 Hz, 1 H) 3.91 (s, 3 H) 4.66 (t, J=5.38 Hz, 2 H) 4.80 (t, J=5.28 Hz, 2 H) 5.46-5.56 (m, 1 H) 6.68 (d, J=5.28 Hz, 1 H) 7.00-7.09 (m, 2 H) 7.34 (d, J=2.35 Hz, 1 H) 7.52 (d, J=8.22 Hz, 1 H) 7.59-7.66 (m, 2 H) 7.84 (d, J=1.96 Hz, 1 H) 7.99 (d, J=9.19 Hz, 1 H) 8.64 (d, J=5.28 Hz, 1 H). 19F NMR (377 MHz, CHLOROFORM-d) δ ppm −73.59 (d, J=8.01 Hz, 3 F).

Workup

  1. customwas sparged with argon for 5 minutes
  2. customwas then partitioned between 9:1 CHCl3/IPA (25 mL) and 5% NaHCO3 (10 mL)
  3. dry with materialThe organic layer was then dried over MgSO4
  4. concentrationconcentrated
  5. custompurified on silica (40 g)
  6. washeluting with 2 to 3% MeOH/DCM
  7. customProduct was isolated as an off white solid from ACN

Sources & evidence

ORD record
ord-8fbf43cbfdea43eaa5ea350b7843ac4e
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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