Sodium Carbonate → HCID 90425181, compound

HRID 527460Notes

Reaction equation

HRID 527460 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:15])[CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[C:4]([Cl:16])[N:3]=1.C([O-])([O-])=O.[Na+].[Na+].[C:23]([O:27][C:28](=[O:58])[N:29]([CH2:31][CH:32]([O:50][Si:51]([C:54]([CH3:57])([CH3:56])[CH3:55])([CH3:53])[CH3:52])[CH2:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=1)[CH3:30])([CH3:26])([CH3:25])[CH3:24]>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:23]([O:27][C:28](=[O:58])[N:29]([CH2:31][CH:32]([O:50][Si:51]([C:54]([CH3:57])([CH3:56])[CH3:55])([CH3:52])[CH3:53])[CH2:33][O:34][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]([C:2]2[N:3]=[C:4]([Cl:16])[CH:5]=[C:6]([N:8]([CH3:15])[CH:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)[N:7]=2)[CH:40]=1)[CH3:30])([CH3:24])([CH3:26])[CH3:25]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 90425334HCID 90425334, compoundHCID 90425669HCID 90425669, compound

Product 1

HCID 90425181HCID 90425181, compoundYield 44.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of (2,6-dichloro-pyrimidin-4-yl)-methyl-(tetrahydro-pyran-4-yl)amine (0.4 g, 1.5 mmol) in degassed dioxane and H2O (4/1, 25 mL) was added Na2CO3 (315 mg, 3.0 mmol); Pd(PPh3)4 (86 mg, 0.075 mmol) and {2-(tert-Butyl-dimethyl-silanyloxy)-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-propyl}-methyl-carbamic acid tert-butyl ester (703 mg, 1.35 mmol). The system was purged with N2 stream and the mixture was stirred at 100° C. for 2 h., cooled to room temperature, diluted with water (50 mL) and extracted with EtOAc (50 mL×2). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by preparative HPLC to give [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 (373 mg, 40% yield) as major product. ESI-LCMS (m/z): 411.2 [M+1]+along with the minor product [2-(tert-Butyl-dimethyl-silanyloxy)-3-(3-{2-chloro-6-[methyl-(tetrahydro-pyran-4-yl)-amino]-pyrimidin-4-yl}-phenoxy)-propyl]-methyl-carbamic acid tert-butyl ester (140 mg, 15% yield). ESI-LCMS (m/z): 411.2 [M+1]+.

Workup

  1. customThe system was purged with N2 stream
  2. temperaturecooled to room temperature
  3. additiondiluted with water (50 mL)
  4. extractionextracted with EtOAc (50 mL×2)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-64a0cfa8ccd54ea08a142aca58aed90c
Source dataset
uspto-grants-2016_05
Patent number
US09346802B2

Reaction notes

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