Water → 4-(1,2-Dimethylimidazol-5-yl)-2-(4-(fluorosulphonyl)anilino)pyrimidine

HRID 1064335Notes

Reaction equation

HRID 1064335 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[N:13]=[C:12]([C:14]2[N:18]([CH3:19])[C:17]([CH3:20])=[N:16][CH:15]=2)[CH:11]=[CH:10][N:9]=1.I[C:22]1[CH:27]=[CH:26][C:25]([S:28]([F:31])(=[O:30])=[O:29])=[CH:24][CH:23]=1.O>O1CCOCC1.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].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:19][N:18]1[C:14]([C:12]2[CH:11]=[CH:10][N:9]=[C:8]([NH:7][C:22]3[CH:27]=[CH:26][C:25]([S:28]([F:31])(=[O:30])=[O:29])=[CH:24][CH:23]=3)[N:13]=2)=[CH:15][N:16]=[C:17]1[CH3:20]

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 2327404-Iodobenzene-1-sulfonyl fluorideHCID 222735092-Amino-4-(1,2-dimethylimidazol-5-yl)pyrimidine

Product 1

HCID 222735054-(1,2-Dimethylimidazol-5-yl)-2-(4-(fluorosulphonyl)anilino)pyrimidineYield 71%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Caesium carbonate (2.3 g, 7.2 mmol) was added to a degassed solution of 2-amino-4-(1,2-dimethylimidazol-5-yl)pyrimidine (Method 26; 756 mg, 4 mmol), 4-iodosulphonyl fluoride (Method 58; 1.50 g, 5.2 mmol), tris(dibenzylideneacetone)dipalladium (0) (92 mg, 0.18 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (124 mg, 0.18 mmol) in dioxane (36 ml) under nitrogen. The mixture was heated at 80° C. for 18 hours and then allowed to cool to ambient temperature. The mixture was poured into water (50 ml) and extracted with DCM (2×50 ml). The organic extracts were combined, washed with brine (50 ml), dried and the solvent evaporated. The residue was pre-absorbed on to silica gel and purified by column chromatography on silica gel eluting with DCM/2% methanolic ammonia (100:0 increasing in polarity to 97:3) to give the title compound (984 mg, 71%) as a pale yellow solid. NMR 2.38 (s, 3H), 3.96 (s, 3H), 7.28 (d, 1H), 7.65 (s, 1H), 8.00 (d, 2H), 8.13 (s, 2H), 8.47 (d, 1H), 10.32 (s, 1H); m/z 348.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionextracted with DCM (2×50 ml)
  3. washwashed with brine (50 ml)
  4. customdried
  5. customthe solvent evaporated
  6. customThe residue was pre-absorbed on to silica gel
  7. custompurified by column chromatography on silica gel eluting with DCM/2% methanolic ammonia (100:0 increasing in polarity to 97:3)

Sources & evidence

ORD record
ord-7c4fb19ad64e460ca61303b00771ddb3
Source dataset
uspto-grants-2005_11
Patent number
US06969714B2

Reaction notes

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