Sodium Carbonate → HCID 131735894, compound

HRID 2207370Notes

Reaction equation

HRID 2207370 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Br[C:8]1[CH:9]=[CH:10][C:11]([C:14]([OH:25])([CH3:24])[CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])=[N:12][CH:13]=1.[CH3:26][C:27]1[CH:28]=[C:29]([NH:42][C:43]2[N:48]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:46]=[CH:45][N:44]=2)[CH:30]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:32]=1>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].ClCCl>[Si:17]([O:16][CH2:15][C:14]([C:11]1[CH:10]=[CH:9][C:8]([C:31]2[CH:30]=[C:29]([NH:42][C:43]3[N:48]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:46]=[CH:45][N:44]=3)[CH:28]=[C:27]([CH3:26])[CH:32]=2)=[CH:13][N:12]=1)([OH:25])[CH3:24])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 131735893HCID 131735893, compound

Product 1

HCID 131735894HCID 131735894, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

2-Methyl-THF (1.48 mL), sodium carbonate (2M, 223 μL, 0.446 mmol) and 2-(5-bromopyridin-2-yl)-1-{[tert-butyl(dimethyl)silyl]oxy}propan-2-ol (170 mg, 0.490 mmol) were added to N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (169 mg, 0.446 mmol) and purged and flushed with Ar(g) (3×). PdCl2(dppf)-dichloromethane adduct (18.2 mg, 0.022 mmol) was added to the reaction mixture, purged and flushed with Ar(g) (3×) and heated to 85° C. for 2 hours. The reaction was cooled to room temperature and was diluted with water (5.00 mL), extracted with DCM (5.00 mL), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (acetone/hexanes) to yield 1-{[tert-butyl(dimethyl)silyl]oxy}-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propan-2-ol. The isolated intermediate was dissolved in neat TFA (1.00 mL) and stirring for 20 minutes at room temperature. The excess TFA was removed under reduced pressure and the resultant residue was partitioned with dichloromethane (5.00 mL) and 1M NaOH (aq) (5.00 mL). The organic layer was washed with brine (5.00 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (acetone/hexanes) to yield 2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propane-1,2-diol. MS APCI calc'd for C20H20F3N4O2 [M+H]+ 405. found 405. 1H NMR (500 MHz, DMSO-d6) δ 10.27 (s, 1H), 8.83 (d, J=5.5 Hz, 1H), 8.72 (s, 1H), 7.96 (d, J=16.2 Hz, 1H), 7.70 (d, J=9.2 Hz, 1H), 7.55 (s, 1H), 7.27 (d, J=5.5 Hz, 1H), 7.18 (s, 1H), 5.13 (s, 1H), 4.64 (s, 1H), 3.57 (d, J=7.6 Hz, 2H), 2.36 (s, 3H), 1.40 (s, 3H).

Workup

  1. custompurged
  2. customflushed with Ar(g) (3×)
  3. custompurged
  4. customflushed with Ar(g) (3×)
  5. temperatureThe reaction was cooled to room temperature
  6. additionwas diluted with water (5.00 mL)
  7. extractionextracted with DCM (5.00 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (acetone/hexanes)

Sources & evidence

ORD record
ord-91f00467b8284f65a48fe22d1fe7845f
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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