1-(5-(6-Amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone → 2-(5-(6-Amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)propan-2-ol

HRID 1621977Notes

Reaction equation

HRID 1621977 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:10]=[C:11]([C:25](=[O:27])[CH3:26])[CH:12]=[N:13][C:14]=2[NH:15][C:16]2[CH:17]=[N:18][C:19]([O:23][CH3:24])=[C:20]([F:22])[CH:21]=2)[CH:3]=1.[CH3:28][Mg]Br>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:10]=[C:11]([C:25]([OH:27])([CH3:28])[CH3:26])[CH:12]=[N:13][C:14]=2[NH:15][C:16]2[CH:17]=[N:18][C:19]([O:23][CH3:24])=[C:20]([F:22])[CH:21]=2)[CH:3]=1

Participants

4

Reactant 2

HCID 666003541-(5-(6-Amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanoneHCID 178418573HCID 178418573, compound

Product 1

HCID 595483392-(5-(6-Amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)propan-2-olYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 1-(5-(6-amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (88 mg, 0.24 mmol) in 2 mL of THF at 0° C. was treated with methylmagnesium bromide (0.55 mL of 3.0 M solution in diethyl ether, 1.67 mmol). It was stirred at 0° C. for 15 min, and quenched with 5 mL of sat. NH4Cl. The mixture was extracted with 2×15 mL of EtOAc. The organic extracts were dried and concentrated. The crude material was purified on a silica gel column and eluted with 20-70% EtOAc in DCM to give 2-(5-(6-amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)propan-2-ol (58 mg, 63% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.23 (s, 1H), 8.35 (m, 1H), 8.32 (d, J=2.2 Hz, 1H), 8.17 (m, 2H), 7.02 (br, 2H), 6.03 (s, 1H), 5.18 (s, 1H), 3.92 (s, 3H), 2.47 (s, 3H), 1.48 (s, 6H). m/z (ESI, positive ion) 385.2 (M+H)+.

Workup

  1. customquenched with 5 mL of sat. NH4Cl
  2. extractionThe mixture was extracted with 2×15 mL of EtOAc
  3. customThe organic extracts were dried
  4. concentrationconcentrated
  5. customThe crude material was purified on a silica gel column
  6. washeluted with 20-70% EtOAc in DCM

Sources & evidence

ORD record
ord-c66a57636e2d4ca994ec7d65fcab46ae
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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