Sodium bis(trimethylsilyl)amide → 4-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812309Notes

Reaction equation

HRID 1812309 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Si:11]([O:18][CH2:19][C:20]([C:23]1[CH:24]=[C:25]([C:30]2[N:35]=[C:34]([CH3:36])[N:33]=[C:32]([NH2:37])[N:31]=2)[C:26](F)=[N:27][CH:28]=1)([CH3:22])[CH3:21])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].[F:38][C:39]1[CH:40]=[C:41]([NH2:47])[CH:42]=[N:43][C:44]=1[O:45][CH3:46]>C1COCC1>[Si:11]([O:18][CH2:19][C:20]([C:23]1[CH:24]=[C:25]([C:30]2[N:35]=[C:34]([CH3:36])[N:33]=[C:32]([NH2:37])[N:31]=2)[C:26]([NH:47][C:41]2[CH:42]=[N:43][C:44]([O:45][CH3:46])=[C:39]([F:38])[CH:40]=2)=[N:27][CH:28]=1)([CH3:21])[CH3:22])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 454803515-Fluoro-6-methoxypyridin-3-amineHCID 666114554-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666117214-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium bis(trimethylsilyl)amide (1.0M in THF) (Aldrich, St. Louis, Mo.; 0.447 mL, 0.447 mmol) was added to an orange-brown solution of 4-(5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (73.0 mg, 0.186 mmol) and 5-fluoro-6-methoxypyridin-3-amine (Anichem, North Brunswick, N.J.; 31.8 mg, 0.224 mmol) in THF (2.0 mL) at 0° C., and the resulting brown solution was stirred at 0° C. for 1 h. Excess sodium bis(trimethylsilyl)amide was carefully quenched with saturated aqueous NH4Cl (5 mL), and the resulting mixture was partitioned between CH2Cl2 (50 mL) and half-saturated aqueous NH4Cl (30 mL). The aqueous layer was extracted with CH2Cl2 (30 mL), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0 to 70% EtOAc/hexanes) furnished 4-(5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (88.8 mg, 0.173 mmol, 93% yield) as a yellow-orange solid. m/z (ESI, +ve) 514.0 (M+H)+.

Workup

  1. customExcess sodium bis(trimethylsilyl)amide was carefully quenched with saturated aqueous NH4Cl (5 mL)
  2. customthe resulting mixture was partitioned between CH2Cl2 (50 mL) and half-saturated aqueous NH4Cl (30 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (30 mL)
  4. dry with materialthe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel, 0 to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2ead7fddfaed41c5ac96124c2340c632
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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