Sodium Carbonate → HCID 90425445, compound

HRID 527461Notes

Reaction equation

HRID 527461 reaction equation
[C:1]([O:5][C:6](=[O:42])[N:7]([CH2:9][CH:10]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]2[N:24]=[C:23](Cl)[CH:22]=[C:21]([N:26]([CH3:33])[CH:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:20]=2)[CH:14]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[N:49]1[CH:54]=[CH:53][C:52](B(O)O)=[CH:51][CH:50]=1>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:42])[N:7]([CH2:9][CH:10]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]2[N:20]=[C:21]([N:26]([CH3:33])[CH:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:22]=[C:23]([C:52]3[CH:53]=[CH:54][N:49]=[CH:50][CH:51]=3)[N:24]=2)[CH:14]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 90425181HCID 90425181, compound

Product 1

HCID 90425445HCID 90425445, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [2-(tert-Butyl-dimethyl-silanyloxy)-3-(3-{4-chloro-6-[methyl-(tetrahydro-pyran-4-yl)-amino]-pyrimidin-2-yl}-phenoxy)-propyl]-methyl-carbamic acid tert-butyl ester (160 mg, 0.26 mmol) in degassed dioxane and H2O (4/1, 25 mL) was added Na2CO3 (83 mg, 0.78 mmol); Pd(PPh3)4 (30 mg, 0.026 mmol) and pyridin-4-ylboronic acid (64 mg, 0.52 mmol). The system was purged with N2 stream and the mixture was stirred 100° C. for 2 h., cooled down to room temperature, diluted with water (25 mL) and extracted with EtOAc (25 mL×2). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by chromatographic column on silica gel (petroleum ether/EtOAc=10/1 to 1/1) to give [2-(tert-Butyl-dimethyl-silanyloxy)-3-(3-{4-[methyl-(tetrahydro-pyran-4-yl)-amino]-6-pyridin-4-yl-pyrimidin-2-yl}-phenoxy)-propyl]-methyl-carbamic acid tert-butyl ester (128 mg, 75% yield). ESI-LCMS (m/z): 664.4 [M+1]+.

Workup

  1. customThe system was purged with N2 stream
  2. temperaturecooled down to room temperature
  3. additiondiluted with water (25 mL)
  4. extractionextracted with EtOAc (25 mL×2)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatographic column on silica gel (petroleum ether/EtOAc=10/1 to 1/1)

Sources & evidence

ORD record
ord-c5c2f2ee255b4291a0f151110bb6a5aa
Source dataset
uspto-grants-2016_05
Patent number
US09346802B2

Reaction notes

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