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

HRID 410418Notes

Reaction equation

HRID 410418 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].Cl[C:15]1[N:20]=[C:19]([C:21]2[N:22]=[N:23][N:24]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[CH:25]=2)[CH:18]=[CH:17][N:16]=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-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][N:24]2[CH:25]=[C:21]([C:19]3[CH:18]=[CH:17][N:16]=[C:15]([NH:5][C:4]4[CH:6]=[C:7]([C:9]5[S:13][CH:12]=[N:11][CH:10]=5)[CH:8]=[C:2]([CH3:1])[CH:3]=4)[N:20]=3)[N:22]=[N:23]2)=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58456365HCID 58456365, compoundHCID 772310702-chloro-4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]pyrimidine

Product 1

HCID 584563154-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amineYield 33.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of 3-methyl-5-(1,3-thiazol-5-yl)aniline (63 mg, 0.33 mmol) and the product of Step 1 (100 mg, 0.33 mmol) in degassed 1,4-dioxane (1.3 mL) were added Pd(OAc)2 (7.4 mg, 0.033 mmol), Xantphos (29 mg, 0.050 mmol) and Cs2CO3 (216 mg, 0.66 mmol) and the reaction was heated to 100° C. for 30 minutes. After cooling, the reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate (10 mL). The layers were separated, and the aqueous phase was extracted with EtOAc (10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (10 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. Purification on silica (30-70% ethyl acetate in hexanes) afforded 4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (50 mg, 33%) as a colorless foam. MS ESI: [M+H]+ m/z 456.1.

Workup

  1. temperatureAfter cooling
  2. customthe reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (10 mL)
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride (10 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification on silica (30-70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1b0a3854d4244bf09895a5775f1c20a4
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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