Lithium iodide → 4-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)pyrimidine

HRID 1498806Notes

Reaction equation

HRID 1498806 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[CH2:6][C:7]1[N:11]([C:12]2[CH:17]=[C:16]([CH:18]=[CH2:19])[N:15]=[C:14]([CH3:20])[N:13]=2)[N:10]=[C:9]([CH3:21])[N:8]=1.Cl[CH:28](Cl)[B:29]1[O:33][C:32]([CH3:35])([CH3:34])[C:31]([CH3:37])([CH3:36])[O:30]1.[I-].[Li+]>O1CCCC1.[Cl-].[Cr+2].[Cl-]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[CH2:6][C:7]1[N:11]([C:12]2[CH:17]=[C:16]([CH:18]3[CH2:19][CH:28]3[B:29]3[O:33][C:32]([CH3:35])([CH3:34])[C:31]([CH3:37])([CH3:36])[O:30]3)[N:15]=[C:14]([CH3:20])[N:13]=2)[N:10]=[C:9]([CH3:21])[N:8]=1

Participants

6

Reactant 3

HCID 66321Lithium iodideHCID 110420412-(Dichloromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 715484294-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-vinylpyrimidine

Product 1

HCID 867320684-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)pyrimidine

Reagents, catalysts & solvents 2

HCID 10197677chromium(II) dichlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirring slurry of chromium(II) chloride (630 mg, 5.12 mmol, 8.0 eq.) in dry tetrahydrofuran (10 ml) under nitrogen at 23° C. was added n,n,n′,n′-tetramethylethylenediamine (0.768 ml, 5.12 mmol, 8.0 eq.). The resulting blue reaction mixture was allowed to stir for 20 min. To the reaction mixture was added a solution of 4-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-vinylpyrimidine (3-1, 225 mg, 0.640 mmol, 1.0.eq.) in tetrahydrofuran (2 mL) followed by a solution of 2-(dichloromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (270 mg, 1.281 mmol, 2.0 eq.) and lithium iodide (343 mg, 2.56 mmol, 4.0 eq) in tetrahydrofuran (2 mL). The resulting greenish blue reaction mixture was allowed to stir for 72 h. The reaction mixture was filtered, concentrated, and partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated to afford 4-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)pyrimidine (3-2). The crude material was carried forward with no purification. LRMS m/z (M+H) 492.5 found, 492.3 required

Workup

  1. customThe resulting greenish blue reaction mixture
  2. stirringto stir for 72 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. custompartitioned between ethyl acetate (100 mL) and water (100 mL)
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-71619895d0c54f9893fb7a84fcd3cf86
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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