Tetrahydrofuran → HCID 66611181, compound

HRID 1621922Notes

Reaction equation

HRID 1621922 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:10])[CH:5]=[N:6][C:7]=1[O:8][CH3:9].[CH3:11][O:12][C:13]1[CH:49]=[CH:48][C:16]([CH2:17][N:18]([CH2:39][C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=2)[C:19]2[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([C:26]3[CH:27]=[C:28]([CH:33]([OH:38])[C:34]([F:37])([F:36])[F:35])[CH:29]=[N:30][C:31]=3F)[N:20]=2)=[CH:15][CH:14]=1.C1COCC1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][N:18]([CH2:39][C:40]2[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=2)[C:19]2[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([C:26]3[CH:27]=[C:28]([CH:33]([OH:38])[C:34]([F:35])([F:36])[F:37])[CH:29]=[N:30][C:31]=3[NH:10][C:4]3[CH:5]=[N:6][C:7]([O:8][CH3:9])=[C:2]([F:1])[CH:3]=3)[N:20]=2)=[CH:48][CH:49]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 454803515-Fluoro-6-methoxypyridin-3-amineHCID 66611623HCID 66611623, compound

Product 1

HCID 66611181HCID 66611181, compoundYield 91%

Procedure

To a stirred mixture of 5-fluoro-6-methoxypyridin-3-amine (2.427 g, 17.07 mmol) and 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)-2,2,2-trifluoroethanol (4.64 g, 8.54 mmol) in THF (50.00 mL, 610 mmol) was added LiHMDS (1.0 M in THF, Aldrich; 42.7 mL, 42.7 mmol) dropwise at −10° C. and the mixture was stirred at the same temperature for 30 min. The reaction was quenched with water and saturated NH4Cl(aq)(25 mL each) and diluted with EtOAc (25 mL). The separated aqueous layer was extracted with ethyl acetate (2×50 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a crude residue which was purified by flash column chromatography (ISCO Combiflash system, 0% to 50% ethyl acetate in hexanes) to obtain the desired product 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2,2,2-trifluoroethanol (5.1428 g, 7.73 mmol, 91% yield) as a brown foam.

Workup

  1. customThe reaction was quenched with water and saturated NH4Cl(aq)(25 mL each)
  2. additiondiluted with EtOAc (25 mL)
  3. extractionThe separated aqueous layer was extracted with ethyl acetate (2×50 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give a crude residue which
  8. customwas purified by flash column chromatography (ISCO Combiflash system, 0% to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-15ebb3abc77741c7a11fb0deba9f3a0e
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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