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

HRID 1621810Notes

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)[N: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)[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of 1-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (140 mg, 0.38 mmol) in THF (2 mL) at 0° C. was treated with methylmagnesium bromide (1.9 mL of 1.4 M in toluene/THF=75/25, 2.65 mmol). The reaction mixture was stirred at 0° C. for 5 min followed by RT for 30 min and then quenched with sat. NH4Cl solution and extracted with EtOAc. The organic layer was concentrated and purified on a silica gel column eluting with 5-10% MeOH in DCM to give 2-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)propan-2-ol (50 mg, 34%) as a yellow crystalline solid. m/z (ESI, +ve ion) 386.0 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.91 (br., 1H); 8.95 (d, J=2.6 Hz, 1H); 8.43-8.37 (m, 3H); 7.89 (s, 1H); 7.73 (s, 1H); 5.15 (s, 1H); 3.93 (s, 3H); 2.45 (s, 3H); 1.47 (s, 6H).

Workup

waitfollowed by RT for 30 min
customquenched with sat. NH4Cl solution
extractionextracted with EtOAc
concentrationThe organic layer was concentrated
custompurified on a silica gel column
washeluting with 5-10% MeOH in DCM

Sources & evidence

ORD record: ord-018b79f8804a45e48a5f0cd8a4ea446e
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772480B2

Reaction notes

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