Lithium Hexamethyldisilazide → HCID 66600285, compound

HRID 1621614Notes

Reaction equation

HRID 1621614 reaction equation
[F:1][CH:2]([F:11])[O:3][C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7].F[C:13]1[C:18]([C:19]2[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([N:26]([CH2:36][C:37]3[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=3)[CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[N:20]=2)=[CH:17][CH:16]=[CH:15][N:14]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:1][CH:2]([F:11])[O:3][C:4]1[CH:5]=[C:6]([NH:7][C:13]2[C:18]([C:19]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([N:26]([CH2:27][C:28]4[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=4)[CH2:36][C:37]4[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=4)[N:20]=3)=[CH:17][CH:16]=[CH:15][N:14]=2)[CH:8]=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27741103-(Difluoromethoxy)anilineHCID 595482404-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 66600285HCID 66600285, compoundYield 102.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-(difluoromethoxy)aniline (0.038 mL, 0.303 mmol) (Aldrich) and 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.090 g, 0.202 mmol) in THF (3.0 mL) at 0° C. was treated with LiHMDS 1.0 M in THF (0.606 mL, 0.606 mmol) (Aldrich) dropwise. The solution was stirred at 0° C. for 1.5 h and was then quenched with a saturated solution of NH4Cl at 0° C. The mixture was extracted with EtOAc (15 mL), dried over MgSO4, filtered and concentrated to give 4-(2-(3-(difluoromethoxy)phenylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.121 g, 0.207 mmol, 99% yield) as a brown oil. 1H NMR (400 MHz, CDCl3) δ 12.12 (br. s., 1H); 8.84 (d, J=8.2 Hz, 1H); 8.35 (br. s., 1H); 7.72 (br. s., 1H); 7.31 (d, J=8.4 Hz, 1H); 7.20 (d, J=7.8 Hz, 5H); 7.11 (t, J=8.0 Hz, 4H); 6.84-6.90 (m, 4H); 6.80 (d, J=7.8 Hz, 1H); 6.71 (d, J=8.4 Hz, 1H); 6.65 (br. s., 1H); 6.45-6.54 (m, 10H); 6.42 (br. s., 4H); 6.28 (br. s., 1H); 4.84 (br. s., 4H); 3.80 (d, J=3.5 Hz, 7H); 2.60 (br. s., 3H). m/z (ESI, +ve ion) 585.1 (M+H)+.

Workup

  1. customwas then quenched with a saturated solution of NH4Cl at 0° C
  2. extractionThe mixture was extracted with EtOAc (15 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-519670e86bf347d09bd1514beb790495
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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