Sodium Carbonate → HCID 73386980, compound

HRID 1480781Notes

Reaction equation

HRID 1480781 reaction equation
Cl[C:2]1[C:7]2[N:8]=[C:9]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=4)=[CH:15][C:14]=3[O:25][CH3:26])[N:10]=[CH:11][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH2:27]([N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1)[CH3:28].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:27]([N:29]1[CH:33]=[C:32]([C:2]2[C:7]3[N:8]=[C:9]([NH:12][C:13]4[CH:18]=[CH:17][C:16]([C:19]5[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=5)=[CH:15][C:14]=4[O:25][CH3:26])[N:10]=[CH:11][C:6]=3[CH:5]=[CH:4][N:3]=2)[CH:31]=[N:30]1)[CH3:28]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 89995981HCID 89995981, compound

Product 1

HCID 73386980HCID 73386980, compoundYield 69.1%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8-chloro-N-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)pyrido[3,4-d]pyrimidin-2-amine (Example 94, 35 mg, 0.095 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (32 mg, 0.144 mmol) and Pd(dppf)Cl2.DCM (8 mg, 9.79 μmol) was dissolved in THF (0.6 mL) and 2M sodium carbonate in water (0.2 mL) and heated to 65° C. for 18 hours. The mixture was diluted with DCM and quenched with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM three times. The combined organic layers were dried and concentrated. The residue was purified by silica gel column chromatography eluting with 0 to 5% MeOH in EtOAc to give the title compound (28 mg, 68%).

Workup

  1. customquenched with saturated aqueous NaHCO3
  2. extractionThe aqueous layer was extracted with DCM three times
  3. customThe combined organic layers were dried
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with 0 to 5% MeOH in EtOAc

Sources & evidence

ORD record
ord-82915b2fca904bfb8c43c183f04c90bf
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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