Lithium Hexamethyldisilazide → HCID 66611533, compound

HRID 1812190Notes

Reaction equation

HRID 1812190 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][O:8][C:9]2[CH:14]=[C:13]([NH2:15])[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:29]1[C:34]([C:35]2[N:40]=[C:39]([CH3:41])[N:38]=[C:37]([N:42]([CH2:52][C:53]3[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=3)[CH2:43][C:44]3[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=3)[N:36]=2)=[CH:33][CH:32]=[CH:31][N:30]=1>C1COCC1>[CH3:60][O:59][C:56]1[CH:55]=[CH:54][C:53]([CH2:52][N:42]([CH2:43][C:44]2[CH:45]=[CH:46][C:47]([O:50][CH3:51])=[CH:48][CH:49]=2)[C:37]2[N:36]=[C:35]([C:34]3[C:29]([NH:15][C:13]4[CH:12]=[CH:11][N:10]=[C:9]([O:8][CH2:7][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:17][CH:16]=5)[CH:14]=4)=[N:30][CH:31]=[CH:32][CH:33]=3)[N:40]=[C:39]([CH3:41])[N:38]=2)=[CH:58][CH:57]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 595482404-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 61709251HCID 61709251, compound

Product 1

HCID 66611533HCID 66611533, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-(4-methoxybenzyloxy)pyridin-4-amine (0.500 g, 2.171 mmol) in THF (10 mL) was cooled to 0° C. under N2. Lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (Aldrich) (6.51 mL, 6.51 mmol) was added dropwise and the mixture was stirred at 0° C. for 30 min. 4-(2-Fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.161 g, 2.61 mmol) was added to this reaction mixture. After the addition, the resulting mixture was stirred at 0° C. for 10 min and then removed from the ice bath and stirred for 2 h at rt. The reaction was quenched with water. The resulting mixture was partitioned between EtOAc and sat. NH4Cl. The organic layer was washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (120 g, 20% to 30% EtOAc in hexanes) to give the product as a white solid (0.950 g). m/z (ESI, +ve ion) 656.0 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 12.36 (s, 1H); 8.85 (d, J=7.75 Hz, 1H); 8.40 (d, J=4.38 Hz, 1H); 7.98 (d, J=5.41 Hz, 1H); 7.50 (s, 1H); 7.43 (d, J=8.33 Hz, 2H); 7.21 (d, J=8.18 Hz, 4H); 7.02 (d, J=4.38 Hz, 1H); 6.73-6.98 (m, 7H); 5.32 (s, 2H); 4.85 (br. s., 4H); 3.69-3.96 (m, 9H); 2.62 (s, 3H).

Workup

  1. additionAfter the addition
  2. stirringthe resulting mixture was stirred at 0° C. for 10 min
  3. customremoved from the ice bath
  4. stirringstirred for 2 h at rt
  5. customThe reaction was quenched with water
  6. customThe resulting mixture was partitioned between EtOAc and sat. NH4Cl
  7. washThe organic layer was washed with water, brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography (120 g, 20% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3f9293933e464a25834453df9c5e4603
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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