Cesium carbonate → 4-cyclopropyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine

HRID 1040069Notes

Reaction equation

HRID 1040069 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([C:9]2[S:13][CH:12]=[N:11][CH:10]=2)[CH:8]=1)[NH2:5].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:21]1[N:26]=[C:25]([CH:27]2[CH2:29][CH2:28]2)[CH:24]=[CH:23][N:22]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:27]1([C:25]2[CH:24]=[CH:23][N:22]=[C:21]([NH:5][C:4]3[CH:6]=[C:7]([C:9]4[S:13][CH:12]=[N:11][CH:10]=4)[CH:8]=[C:2]([CH3:1])[CH:3]=3)[N:26]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 249019152-Chloro-4-cyclopropylpyrimidine2×HCID 58456365HCID 58456365, compound

Product 1

HCID 584561394-cyclopropyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amineYield 74.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 20 mL microwave vial was charged with 3-methyl-5-(1,3-thiazol-5-yl)aniline (500 mg, 2.63 mmol), cesium carbonate (2.99 g, 9.20 mmol), 2-chloro-4-cyclopropylpyrimidine (Intermediate 29, 406 mg, 2.63 mmol), and dioxane (10.4 mL). The system was purged and flushed with argon (3×) before adding XantPhos (228 mg, 0.394 mmol) and palladium(II) acetate (59 mg, 0.263 mmol). The system was then purged and flushed with argon (3×) before sealing and heating to 100° C. for 2 h. Upon completion the mixture was cooled to room temperature, diluted with ethyl acetate, filtered through celite washing with ethyl acetate, and concentrated under reduced pressure. Purification by column chromatography on silica gel (0-60% ethyl acetate in hexanes) provided 603 mg (1.96 mmol, 74%) of 4-cyclopropyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine as a yellow solid. MS ESI: [M+H]+ m/z 309.2.

Workup

  1. customThe system was purged
  2. customflushed with argon (3×)
  3. customThe system was then purged
  4. customflushed with argon (3×)
  5. temperatureUpon completion the mixture was cooled to room temperature
  6. additiondiluted with ethyl acetate
  7. filtrationfiltered
  8. washthrough celite washing with ethyl acetate
  9. concentrationconcentrated under reduced pressure
  10. customPurification by column chromatography on silica gel (0-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3173ab103f0a4ababad871be52ba1011
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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