Cesium carbonate → N-[3-({[tert-butyl(dimethyl)silyl]oxy}-methyl)-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

HRID 410413Notes

Reaction equation

HRID 410413 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([NH:25][C:26]2[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=2)[CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:77]1[S:81][CH:80]=[N:79][CH:78]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([NH:25][C:26]2[N:31]=[C:30]([C:32]([F:34])([F:35])[F:33])[CH:29]=[CH:28][N:27]=2)[CH:13]=[C:14]([C:77]2[S:81][CH:80]=[N:79][CH:78]=2)[CH:15]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 5460595-BromothiazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67431726HCID 67431726, compound

Product 1

HCID 58456077N-[3-({[tert-butyl(dimethyl)silyl]oxy}-methyl)-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amineYield 60%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a flask containing the product of Step 4 (750 mg, 1.47 mmol), dicyclohexyl[2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane (70 mg, 0.15 mmol), Pd2(dba)3 (67 mg, 0.074 mmol), cesium carbonate (959 mg, 2.94 mmol) was added a solution of 5-bromothiazole in a degassed mixture of dioxane (2.7 mL) and water (270 μL). The solution was evacuated and then purged with argon 5 times and then heated at 90° C. overnight. The reaction was cooled, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield N-[3-({[tert-butyl(dimethyl)silyl]oxy}-methyl)-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (414 mg, 0.89 mmol, 60% yield). MS ESI: [M+H]+ m/z 381. 1H NMR (500 MHz, DMSO-d6) δ 10.38 (s, 1H), 9.07 (s, 1H), 8.81 (d, J=4.9, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.69 (s, 1H), 7.28 (d, J=4.9, 1H), 7.26 (s, 1H), 4.72 (s, 2H), 0.91 (s, 9H), 0.09 (s, 6H).

Workup

  1. customThe solution was evacuated
  2. custompurged with argon 5 times
  3. temperatureThe reaction was cooled
  4. additiondiluted with ethyl acetate
  5. washwashed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customFlash chromatography was used for purification

Sources & evidence

ORD record
ord-bac083671eba46b3bb2291f689c68b19
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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