Tetrahydrofuran → 2-{2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6-methyl-pyrimidin-4-yl}-propan-2-ol

HRID 1855467Notes

Reaction equation

HRID 1855467 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[N:21]=[C:20]([C:22](OCC)=O)[CH:19]=[C:18](C)[N:17]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.C[Mg]Cl.[C:31](=O)([O-])[O-].[Na+].[Na+].[O:37]1[CH2:41][CH2:40]CC1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[N:17]=[C:18]([C:41]([OH:37])([CH3:40])[CH3:31])[CH:19]=[C:20]([CH3:22])[N:21]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 10340Sodium CarbonateHCID 57829752HCID 57829752, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 441922492-{2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6-methyl-pyrimidin-4-yl}-propan-2-ol

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6-methyl-pyrimidine-4-carboxylate (184 mg, 0.5 mmol) in tetrahydrofurane (10 mL) was added at 0° C. over 2 min a 3 M solution of methylmagnesiumchloride in tetrahydrofurane (0.55 mL, 1.65 mmol). The reaction mixture was stirred at 0° C. for 15 min followed by 1 h at 20° C. The mixture was poured on saturated sodium carbonate solution (20 mL) and the product was extracted with ethyl acetate (40 mL). The organic layer was washed with brine (20 mL), dried over sodium sulfate and evaporated under reduced pressure. The residual material was crystallized from dichloromethane/heptane to give the title compound to give the title compound (105 mg, 59%) as an off-white solid. MS ISP (m/e): 354.3 [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.76 (d, 1H), 7.63 (s, 1H), 7.18 (d, 1H), 7.02 (dd, 1H), 6.88 (s, 1H), 6.75 (s, 1H), 4.04 (s, 1H), 3.88 (s, 3H), 2.47 (s, 3H), 2.30 (s, 3H), 1.53 (s, 6H).

Workup

  1. waitfollowed by 1 h at 20° C
  2. extractionthe product was extracted with ethyl acetate (40 mL)
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residual material was crystallized from dichloromethane/heptane

Sources & evidence

ORD record
ord-71292290cc284aa186d92ac0ca4734bc
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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