Water → HCID 67491494, compound

HRID 1028446Notes

Reaction equation

HRID 1028446 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18](=[O:34])[C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([O:26][C:27]3[CH:32]=[CH:31][N:30]=[C:29](Cl)[CH:28]=3)[CH:20]=2)[C:8]([O:15][CH3:16])=[C:9]([CH:14]=1)[C:10]([O:12][CH3:13])=[O:11])([CH3:4])([CH3:3])[CH3:2].[K].[C:36]([O:40][C:41]([N:43]1[CH2:48][CH2:47][N:46]([CH2:49][B-](F)(F)F)[CH2:45][CH2:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37].C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCCC1>[C:1]([C:5]1[CH:14]=[C:9]([C:10]([O:12][CH3:13])=[O:11])[C:8]([O:15][CH3:16])=[C:7]([NH:17][C:18]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([CH:20]=2)[O:26][C:27]2[CH:32]=[CH:31][N:30]=[C:29]([CH2:49][N:46]3[CH2:47][CH2:48][N:43]([C:41]([O:40][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:42])[CH2:44][CH2:45]3)[CH:28]=2)=[O:34])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 87420663HCID 87420663, compoundHCID 131731426HCID 131731426, compound

Product 1

HCID 67491494HCID 67491494, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 414 mg methyl 5-tert-butyl-3-[3-(2-chloro-pyridin-4-yloxy)-4-methyl-benzoylamino]-2-methoxy-benzoate, 370 mg potassium-(4-tert-butyloxycarbonyl-piperazin-1-ylmethyl)-trifluoroborate, 0.84 g Cs2CO3, 0.80 ml of water and 8 ml of tetrahydrofuran is flushed for 10 min with argon. Then 200 mg of 2-dicyclohexylphosphinyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (XPhos) and 20 mg palladium(II)acetate are added, and the mixture is heated to 80° C. The reaction mixture is stirred overnight at 80° C. in an argon atmosphere. After cooling to ambient temperature the mixture is evaporated down and the residue is taken up in ethyl acetate and water. The organic phase is separated off, washed with water and aqueous saturated saline solution and dried (MgSO4). The solvent is removed, and the residue is chromatographed on silica gel with dichloromethane/methanol (99:1→90:10) and then chromatographed by reversed phase (HPLC, Xbridge C18) with methanol/water/ammonia.

Workup

  1. customis flushed for 10 min with argon
  2. additionThen 200 mg of 2-dicyclohexylphosphinyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (XPhos) and 20 mg palladium(II)acetate are added
  3. temperatureAfter cooling to ambient temperature the mixture
  4. customis evaporated down
  5. customThe organic phase is separated off
  6. washwashed with water and aqueous saturated saline solution
  7. dry with materialdried (MgSO4)
  8. customThe solvent is removed
  9. customthe residue is chromatographed on silica gel with dichloromethane/methanol (99:1→90:10)
  10. customchromatographed by reversed phase (HPLC, Xbridge C18) with methanol/water/ammonia

Sources & evidence

ORD record
ord-ceda0137d7ae4796b75043b8e678bdf2
Source dataset
uspto-grants-2014_05
Patent number
US08735579B2

Reaction notes

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