1,2-Dimethoxyethane → 2-(2-(4-((6-Amino-3-pyridinyl)sulfonyl)-2-methylphenyl)-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972690Notes

Reaction equation

HRID 1972690 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH2:26])=[N:24][CH:25]=2)(=[O:19])=[O:18])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.Cl[C:28]1[N:33]=[CH:32][C:31]([C:34]([OH:43])([C:39]([F:42])([F:41])[F:40])[C:35]([F:38])([F:37])[F:36])=[CH:30][N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC>O>[NH2:26][C:23]1[N:24]=[CH:25][C:20]([S:17]([C:4]2[CH:5]=[CH:6][C:7]([C:28]3[N:29]=[CH:30][C:31]([C:34]([OH:43])([C:35]([F:36])([F:37])[F:38])[C:39]([F:41])([F:42])[F:40])=[CH:32][N:33]=3)=[C:2]([CH3:1])[CH:3]=2)(=[O:18])=[O:19])=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 665834615-((3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)-2-pyridinamineHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2×

Product 1

HCID 866704402-(2-(4-((6-Amino-3-pyridinyl)sulfonyl)-2-methylphenyl)-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanolYield 25.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 5-((3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)-2-pyridinamine (278 mg, 0.74 mmol), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (139 mg, 0.49 mmol, Intermediate D), (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium (20 mg, 0.025 mmol, Strem Chemical Inc, Newburyport, Mass.), cesium carbonate (484 mg, 1.49 mmol, Sigma-Aldrich, St. Louis, Mo.), DME (1.2 mL), and water (0.1 mL). The reaction mixture was purged with nitrogen for several minutes, and then stirred and heated in an Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 45 min. The organic layer was taken and the solvent was removed under vacuum. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a silica gel column (12 g), eluting with a gradient of DCM to 2% 2M NH3.MeOH in DCM, to provide 2-(2-(4-((6-amino-3-pyridinyl)sulfonyl)-2-methylphenyl)-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol (61 mg) as an off-white solid.

Workup

  1. customA glass microwave reaction vessel
  2. customThe reaction mixture was purged with nitrogen for several minutes
  3. customthe solvent was removed under vacuum
  4. customThe crude material was absorbed onto a plug of silica gel
  5. custompurified by chromatography through a silica gel column (12 g)
  6. washeluting with a gradient of DCM to 2% 2M NH3

Sources & evidence

ORD record
ord-02108fa236fd436eaa64956490a621f9
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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