Sodium bis(trimethylsilyl)amide → HCID 68518770, compound

HRID 1621981Notes

Reaction equation

HRID 1621981 reaction equation
[CH3:1][O:2][C:3]1[CH:43]=[CH:42][C:6]([CH2:7][N:8]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C:23]([CH3:32])([CH3:31])[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:19]=[N:20][C:21]=3F)[N:10]=2)=[CH:5][CH:4]=1.[F:44][C:45]1[CH:46]=[C:47]([NH2:53])[CH:48]=[N:49][C:50]=1[O:51][CH3:52].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>O1CCCC1.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:43]=[CH:42][C:6]([CH2:7][N:8]([CH2:33][C:34]2[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C:23]([CH3:32])([CH3:31])[C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH:19]=[N:20][C:21]=3[NH:53][C:47]3[CH:48]=[N:49][C:50]([O:51][CH3:52])=[C:45]([F:44])[CH:46]=3)[N:10]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 454803515-Fluoro-6-methoxypyridin-3-amineHCID 66611821HCID 66611821, compound

Product 1

HCID 68518770HCID 68518770, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-60 °C

Procedure

Tert-butyl 2-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)-2-methylpropanoate (185 mg, 0.315 mmol) and 5-fluoro-6-methoxypyridin-3-amine (Aldrich; 67.1 mg, 0.472 mmol) were dissolved in tetrahydrofuran (3.1 mL) and the resulting mixture was cooled to −60° C. and sodium bis(trimethylsilyl)amide, 1 M in THF (Aldrich; 944 μL, 0.944 mmol) was added. The resulting mixture was stirred at −60° C. for 1 h, and the reaction mixture was then diluted with 100 mL of EtOAc, added to a separatory funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, and concentrated in vacuo. Chromatographic purification of the residue (silica gel) with 100% hexanes to 50% EtOAc/hexanes to give the title compound (11% yield) as a yellow oil. m/z (ESI, +ve) 709.8 (M+H)+.

Workup

  1. additionadded to a separatory funnel
  2. custompartitioned with sodium bicarbonate (saturated, aqueous)
  3. washwashed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous)
  4. customseparated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel) with 100% hexanes to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-45e4dfbb1bc548ea84a218b86cc7f480
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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