Sodium bis(trimethylsilyl)amide → HCID 86647082, compound

HRID 1621969Notes

Reaction equation

HRID 1621969 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:13]2[N:18]=[C:17]([CH3:19])[N:16]=[C:15]([NH2:20])[N:14]=2)[C:9](F)=[N:10][CH:11]=1)=[CH2:5])C.[Cl:21][C:22]1[N:27]=[CH:26][C:25]([NH2:28])=[CH:24][C:23]=1[O:29][CH3:30].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.CN(C=O)C>[NH2:20][C:15]1[N:16]=[C:17]([CH3:19])[N:18]=[C:13]([C:8]2[CH:7]=[C:6]([C:4](=[O:3])[CH3:5])[CH:11]=[N:10][C:9]=2[NH:28][C:25]2[CH:26]=[N:27][C:22]([Cl:21])=[C:23]([O:29][CH3:30])[CH:24]=2)[N:14]=1

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 234561436-Chloro-5-methoxypyridin-3-amineHCID 666118404-(5-(1-Ethoxyvinyl)-2-fluoropyridin-3-YL)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 86647082HCID 86647082, compoundYield 64.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-(5-(1-ethoxyvinyl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (100 mg, 0.363 mmol) and 6-chloro-5-methoxypyridin-3-amine (Small Molecules, Inc) (86 mg, 0.545 mmol) in 1 mL of THF and 0.3 mL of DMF at 0° C. was added sodium bis(trimethylsilyl)amide (1.09 mL of 1.0 M solution in THF, 1.09 mmol) dropwise and the dark red solution was stirred at this temperature for 30 min. It was quenched with 4 mL of 0.5N HCl and stirred at RT for 10 min. The mixture was treated with 1 N NaOH to pH of about 8. It was extracted twice with EtOAc (30 mL). The combined organic phases were washed with brine and dried over Na2SO4. It was concentrated to half of its volume, the precipitated tan solid was filtered through a fritted funnel, rinsed with 2 mL of ether, collected and dried to give 1-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(6-chloro-5-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (90 mg, 64% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.63 (s, 1H), 9.29 (s, 1H), 9.03 (s, 1H), 8.47 (s, 1H), 8.30 (s, 1H), 8.06 (br., 1H), 7.90 (br., 1H), 3.96 (s, 3H), 2.60 (s, 3H), 2.47 (s, 3H). m/z (ESI, positive ion) 386.0 (M+H)+.

Workup

  1. customIt was quenched with 4 mL of 0.5N HCl
  2. stirringstirred at RT for 10 min
  3. additionThe mixture was treated with 1 N NaOH to pH of about 8
  4. extractionIt was extracted twice with EtOAc (30 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationIt was concentrated to half of its volume
  8. filtrationthe precipitated tan solid was filtered through a fritted funnel
  9. washrinsed with 2 mL of ether
  10. customcollected
  11. customdried

Sources & evidence

ORD record
ord-de04119d664141e79b6e8d61864ecd8c
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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