Cesium carbonate → [4-(4-Imidazo[1,2-alpha]pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone

HRID 19471Notes

Reaction equation

HRID 19471 reaction equation
[N:1]1[CH:2]=[C:3]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.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+].I[C:66]1[CH:71]=[CH:70][C:69]([C:72]([N:74]2[CH2:79][CH2:78][O:77][CH2:76][CH2:75]2)=[O:73])=[CH:68][CH:67]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[N:1]1[CH:2]=[C:3]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:66]3[CH:67]=[CH:68][C:69]([C:72]([N:74]4[CH2:79][CH2:78][O:77][CH2:76][CH2:75]4)=[O:73])=[CH:70][CH:71]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7726344-[(4-Iodophenyl)carbonyl]morpholineHCID 691978644-(Imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine

Product 1

HCID 16667321[4-(4-Imidazo[1,2-alpha]pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone

Reagents, catalysts & solvents 2

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

Procedure

4-Imidazo[1,2-α]pyridin-3-yl-pyrimidin-2-ylamine(Bioorganic & Medicinal Chemistry Letters 2004, 14(9), 2245-2248) (0.20 g, 0.95 mmol), palladium acetate (9 mg, 0.038 mmol), Xanthphos (33 mg, 0.057 mmol), caesium carbonate (0.46 g, 1.4 mmol) and (4-iodo-phenyl)-morpholin-4-yl-methanone (Method 16a in WO 05/044814) (330 mg, 1.05 mmol) were added to dioxane (7 ml) under a inert atmosphere and heated at reflux for 6 hours. Purification on silica using 0-10% MeOH in DCM as eluent gave the title compound as a colourless foam. Further purification was achieved using RPHPLC to give a colourless foam (239 mg, 63%); 1H NMR (400.132 MHz) 10.13 (d, 1H), 9.89 (s, 1H), 8.64 (s, 1H), 8.48 (d, 1H), 7.85 (d, 2H), 7.79 (d, 1H), 7.52 (t, 1H), 7.46 (d, 1H), 7.43 (d, 2H), 7.16 (t, 1H), 3.65-3.60 (m, 4H), 3.58-3.51 (m, 4H); MH+ 401.

Workup

  1. temperatureheated
  2. temperatureat reflux for 6 hours
  3. customPurification on silica using 0-10% MeOH in DCM as eluent

Sources & evidence

ORD record
ord-bb8afc7a752247e9bfa7916dce534294
Source dataset
uspto-grants-2010_06
Patent number
US07745428B2

Reaction notes

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