Potassium Phosphate, Tribasic → HCID 58456183, compound

HRID 410411Notes

Reaction equation

HRID 410411 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([NH:14][C:15]2[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][N:16]=2)[CH:6]=[C:7]([C:9]2[S:13][CH:12]=[N:11][CH:10]=2)[CH:8]=1.[CH:25]1(B(O)O)C[CH2:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2].O.C1(C)C=CC=CC=1>[CH:2]1([C:3]2[CH:4]=[C:5]([NH:14][C:15]3[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][N:16]=3)[CH:6]=[C:7]([C:9]3[S:13][CH:12]=[N:11][CH:10]=3)[CH:8]=2)[CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67257262HCID 67257262, compound

Product 1

HCID 58456183HCID 58456183, compoundYield 81.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a flask were added N-[3-(bromomethyl)-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)-pyrimidin-2-amine (523 mg, 1.30 mmol), cyclopropyl boronic acid (336 mg, 3.91 mmol), potassium phosphate (968 mg, 4.56 mmol), Pd(OAc)2 (15 mg, 0.07 mmol) and tricyclohexylphosphine (37 mg, 0.13 mmol). Degassed toluene (10 mL) and water (0.5 mL) were added and the solution was evacuated and then purged with argon 5 times. The mixture was then heated in the microwave at 130° C. for 30 minutes. The reaction was diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield N-[3-cyclopropyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (384 mg, 1.06 mmol, 81% yield). MS ESI: [M+H]+ m/z 363. 1H NMR (500 MHz, DMSO-d6) δ 10.23 (s, 1H), 9.06 (s, 1H), 8.83 (d, J=4.8, 1H), 8.23 (s, 1H), 7.92 (s, 1H), 7.41 (s, 1H), 7.28 (d, J=4.9, 1H), 7.12 (s, 1H), 2.03-1.80 (m, 1H), 1.05-0.92 (m, 2H), 0.78-0.61 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-a51372537ce24f98a5b7a81f1e0949ac
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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