Cesium carbonate → HCID 67426818, compound

HRID 869295Notes

Reaction equation

HRID 869295 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[N:14]([CH3:30])[C:15](=[O:29])[C:16]([O:19]CC3C=CC(OC)=CC=3)=[CH:17][N:18]=2)[CH:8]=1)(=O)=O.[CH:33]1[C:42]2[CH:41]=[CH:40][CH:39]=[C:38](B(O)O)[C:37]=2[CH:36]=[CH:35][N:34]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:33]1[C:42]2[C:37](=[C:38]([C:7]3[CH:8]=[C:9]([C:13]4[N:14]([CH3:30])[C:15](=[O:29])[C:16]([OH:19])=[CH:17][N:18]=4)[CH:10]=[CH:11][CH:12]=3)[CH:39]=[CH:40][CH:41]=2)[CH:36]=[CH:35][N:34]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 599474Isoquinoline-5-boronic acidHCID 86691087HCID 86691087, compound

Product 1

HCID 67426818HCID 67426818, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 50.0 mg (0.106 mmol) 3-{5-[(4-methoxybenzyl)oxy]-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl}phenyl trifluoromethanesulfonate in 2 ml THF was added 7.8 mg (0.011 mmol) 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane adduct, 18.3 mg (0.106 mmol) isoquinoline-5-boronic acid, and 300 μl (0.300 mmol) 1 M Cs2CO3. The reaction mixture was heated to 120° C. for 20 min in the microwave, then extracted with 10 ml EtOAc, and concentrated in vacuo. The oil was dissolved in 1 ml CH2Cl2, 1 ml TFA was added, and then concentrated in vacuo. Purification by mass-guided high throughput purification gave 15 mg (43% yield) of 2-(3-isoquinolin-5-ylphenyl)-5-hydroxy-3-methylpyrimidin-4(3H)-one. 1H NMR 8 (ppm) (DMSO-d): 9.62 (1H, s), 8.58 (1H, s), 8.34 (1H, d, J=8.04 Hz), 7.97-7.86 (3H, m), 7.74-7.66 (4H, m), 7.57 (1H, s), 2.54 (3H, s). HRMS (ESI positive) calc (M+H)+=330.1237 found 330.1237.

Workup

  1. extractionextracted with 10 ml EtOAc
  2. concentrationconcentrated in vacuo
  3. dissolutionThe oil was dissolved in 1 ml CH2Cl2
  4. addition1 ml TFA was added
  5. concentrationconcentrated in vacuo
  6. customPurification by
  7. custommass-guided high throughput purification

Sources & evidence

ORD record
ord-a2ea079c043a48c7b4e52933c0a28d74
Source dataset
uspto-grants-2015_03
Patent number
US08969364B2

Reaction notes

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