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

HRID 1039903Notes

Reaction equation

HRID 1039903 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 67431726N-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

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 (2704). 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-b66f265f007b46328e016c779dd34a28
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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