Sodium bis(trimethylsilyl)amide → 1-(5-(6-Amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone

HRID 1621976Notes

Reaction equation

HRID 1621976 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])[CH:14]=2)[C:9](F)=[N:10][CH:11]=1)=[CH2:5])C.[F:21][C:22]1[CH:23]=[C:24]([NH2:30])[CH:25]=[N:26][C:27]=1[O:28][CH3:29].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[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:30][C:24]2[CH:25]=[N:26][C:27]([O:28][CH3:29])=[C:22]([F:21])[CH:23]=2)[CH:14]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 454803515-Fluoro-6-methoxypyridin-3-amineHCID 665999816-(5-(1-Ethoxyvinyl)-2-fluoropyridin-3-yl)-2-methylpyrimidin-4-amine

Product 1

HCID 666003541-(5-(6-Amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanoneYield 32.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-(5-(1-ethoxyvinyl)-2-fluoropyridin-3-yl)-2-methylpyrimidin-4-amine (208 mg, 0.76 mmol) and 5-fluoro-6-methoxypyridin-3-amine (162 mg, 1.14 mmol) in 1.5 mL of THF at 0° C. was added sodium bis(trimethylsilyl)amide (1 M in THF) (2.28 mL, 2.28 mmol) dropwise at 0° C. 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 for 10 min. The mixture was basified with 1 N NaOH to pH of 8 and stirred with 10 mL of EtOAc for 5 min. The precipitated brown solid was filtered, washed with 2×2 mL of water followed by 2×2 mL of EtOAc. The brown solid was dried in a vacuum oven at 45° C. for 18 h to give 1-(5-(6-amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (90 mg, 32% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.93 (s, 1H), 8.90 (s, 1H), 8.50 (s, 1H), 8.37 (s, 1H), 8.24 (s, 1H), 7.10 (br., 2H), 6.93 (s, 1H), 3.95 (s, 3H), 2.60 (s, 3H), 1.58 (s, 3H). m/z (ESI, positive ion) 369.0 (M+H)+.

Workup

  1. customIt was quenched with 4 mL of 0.5N HCl
  2. stirringstirred for 10 min
  3. stirringstirred with 10 mL of EtOAc for 5 min
  4. filtrationThe precipitated brown solid was filtered
  5. washwashed with 2×2 mL of water
  6. customThe brown solid was dried in a vacuum oven at 45° C. for 18 h

Sources & evidence

ORD record
ord-7458993069434dd1bfc045dbac8889ac
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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