Diethyl Ether → HCID 59548257, compound

HRID 1621830Notes

Reaction equation

HRID 1621830 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[N:14]=[C:13]([C:15](=[O:17])[CH3:16])[CH:12]=[N:11][C:10]=2[NH:18][C:19]2[CH:20]=[N:21][C:22]([O:26][CH3:27])=[C:23]([F:25])[CH:24]=2)[CH:3]=1.[CH3:28][Mg]Br.C(OCC)C>O1CCCC1.[NH4+].[Cl-]>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[N:14]=[C:13]([C:15]([OH:17])([CH3:28])[CH3:16])[CH:12]=[N:11][C:10]=2[NH:18][C:19]2[CH:20]=[N:21][C:22]([O:26][CH3:27])=[C:23]([F:25])[CH:24]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 66600038HCID 66600038, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 59548257HCID 59548257, compoundYield 74.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1-(6-(6-amino-2-methylpyrimidin-4-yl)-5-(5-fluoro-6-methoxypyridin-3-ylamino)pyrazin-2-yl)ethanone (11 mg, 0.030 mmol) and methylmagnesium bromide, 3.0 M solution in diethyl ether (10.65 μL, 0.089 mmol, Aldrich, St. Louis, Mo.) in tetrahydrofuran (1 mL) was stirred at 0° C. for 30 min. The reaction mixture was diluted with saturated NH4Cl (5 mL) and extracted with CH2Cl2 (2×10 mL). The organic extracts were washed with saturated NaCl 5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography eluting with 5% MeOH/CH2Cl2 to give 2-(6-(6-amino-2-methylpyrimidin-4-yl)-5-(5-fluoro-6-methoxypyridin-3-ylamino)pyrazin-2-yl)propan-2-ol (8.5 mg, 0.022 mmol, 74.1% yield). 1H NMR (300 MHz, CDCl3) δ 1.63 (s, 6H) 2.66 (s, 3H) 3.66 (s, 1H) 4.03 (s, 3H) 5.01 (s, 2H) 7.45 (s, 1H) 8.11 (d, J=1.90 Hz, 1H) 8.22 (dd, J=12.13, 2.05Hz, 1H) 8.39 (s, 1H) 12.66 (s, 1H). m/z (ESI, +ve ion) 386.1 (M+H)+.

Workup

  1. extractionextracted with CH2Cl2 (2×10 mL)
  2. washThe organic extracts were washed with saturated NaCl 5 mL) and
  3. dry with materialdried over Na2SO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo
  6. customto give the crude material as a yellow solid
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-bdc9a9d1b65e4e38a70a9b17a433e78c
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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